Eurozone unemployment heading for 20 million

A demonstrator shouts slogans during the general strike in Pamplona, northern Spain on Thursday, May 30, 2013. People protest against the austerity measures and the strong economic crisis affecting the country with more than six million unemployed. Reading (AP Photo/Alvaro Barrientos)

A demonstrator shouts slogans during the general strike in Pamplona, northern Spain on Thursday, May 30, 2013. People protest against the austerity measures and the strong economic crisis affecting the country with more than six million unemployed. Reading (AP Photo/Alvaro Barrientos)

LONDON (AP) ? Unemployment across the 17 EU countries that use the euro is on course to hit 20 million this year, according to figures showing the jobless rate hit another record high ? the latest ignominious landmark for the currency bloc.

Eurostat, the European Union's statistics office, said Friday that the unemployment rate rose to 12.2 percent in April from the previous record of 12.1 percent the month before.

A net 95,000 people joined the ranks of the unemployed, taking the total to 19.38 million. At this pace, unemployment in the currency bloc ? which has a population of about 330 million ? could breach the 20 million mark this year.

The figures, once again, mask big disparities among the euro countries. While over one in four people are unemployed in Greece and Spain, Germany's rate is stable at a low 5.4 percent.

The differences are particularly stark when looking at the rates of youth unemployment. While Germany's youth unemployment stands at a relatively benign 7.5 percent, well over half of people aged 16 to 25 in Greece and Spain are jobless. Italy's rate has ticked up to over 40 percent.

"Youth joblessness at these levels risks permanently entrenched unemployment, lowering the rate of sustainable growth in the future," said Tom Rogers, senior economic adviser at Ernst & Young.

The differences reflect the varying performance of the euro economies ? Greece, for example, is in its sixth year of a savage recession. Germany's economy has until recently been growing at a healthy pace.

As a whole, the eurozone is in its longest recession since the euro was launched in 1999. The six quarters of economic decline is longer even than the recession that followed the financial crisis of 2008, though it's not as deep.

By contrast the U.S. economy has been growing steadily since the end of its recession in 2009 and the jobs market has started to improve, with the unemployment rate falling to 7.5 percent in April.

Though the eurozone is the epicenter of Europe's debt crisis, other countries in the region are struggling to recover as well. Some, like Britain, are also pursuing deficit reduction measures at a time when demand in their main export market ? the eurozone ? is falling. As a result, the wider 27-nation EU, which includes the non-euro countries such as Britain and Poland, has seen unemployment ratchet higher in recent months. In April it was flat at 11 percent.

One of the reasons behind Europe's economic decline is governments' focus on cutting debt aggressively by raising taxes and slashing spending programs. With many governments still pulling back on spending and business and consumer confidence still low, economists do not expect any dramatic recovery to emerge over the coming months.

The sharpest change in unemployment rates among the 17 euro countries was in Cyprus, which saw its jobless rate rise to 15.6 percent from 14.5 percent.

The small Mediterranean island nation became the fifth euro country to seek financial assistance in March. The difference with the other bailouts was that the country was asked to raise a big chunk of its rescue money from bank depositors ? a shock decision that led to a near two-week shutdown of the banks and battered economic confidence.

The European Central Bank has sought to make life easier for Europe's hard-pressed businesses and consumers by cutting its main interest rate to the record low 0.5 percent earlier this month.

Another cut is possible, but most economists say it's unlikely, even though the inflation rate is still under the ECB's target of just below 2 percent.

Eurostat said Friday that inflation in the eurozone rose to 1.4 percent in the year to May from the 38-month low of 1.2 percent recorded in April. It blamed rising food, alcohol and tobacco prices for the uptick.

Analysts said the ECB is more likely to take measures to shore up lending to small and medium-sized businesses, one of the main job creators in Europe. Such companies are currently not taking out many loans for fear the economy might worsen and because banks are charging high rates.

"So far the ECB's actions have not translated into lower lending rates for businesses and households, failing to boost activity," said Anna Zabrodzka, economist at Moody's Analytics.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/cae69a7523db45408eeb2b3a98c0c9c5/Article_2013-05-31-Europe-Economy/id-be8999c23d3f4d799af635e98303deee

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Power Rankings: May 4, 2013

All WWE programming, talent names, images, likenesses, slogans, wrestling moves, trademarks, logos and copyrights are the exclusive property of WWE, Inc. and its subsidiaries. All other trademarks, logos and copyrights are the property of their respective owners. ? 2013 WWE, Inc. All Rights Reserved. This website is based in the United States. By submitting personal information to this website you consent to your information being maintained in the U.S., subject to applicable U.S. laws. U.S. law may be different than the law of your home country. WrestleMania XXIX (NY/NJ) logo TM & ? 2013 WWE. All Rights Reserved. The Empire State Building design is a registered trademark and used with permission by ESBC.

Source: http://www.wwe.com/inside/power-rankings/power-rankings-may-4-2013

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First black Italian minister seeks cultural change

ROME (AP) ? Italy's first black Cabinet minister, targeted by racist slurs following her appointment last week, said Friday that Italians aren't racist but that some are merely ignorant of other cultures and the "richness" that immigration can bring.

Congolese-born surgeon Cecile Kyenge held a news conference to introduce herself to Italians so they could get to know her.

"I am not 'colored.' I am black. It's important to say that. I emphasize it proudly," she said.

Kyenge's appointment as integration minister had been hailed as a big step for Italy, which has only recently had to cope with waves of immigration and the resulting problems of integration into a largely homogeneous society.

But the move prompted racist taunts from xenophobic politicians and members of neo-fascist Internet groups ? a reaction so vile the government authorized its anti-discrimination office to investigate. (One European parliamentarian from the anti-immigrant Northern League party called her a member of a "bongo bongo government.")

One of her chief defenders, lower house speaker Laura Boldrini, told La Repubblica in an interview posted on its website Friday that she herself has been the target of death threats, which began after she stated publicly that Italy's laws about inciting racial hatred on the Internet should be tightened.

Boldrini showed the newspaper hundreds of printed pages containing the threats that she said showed "'sexist aggression" against her personally, and women in public office in general, ranging from the innocuous to the violent.

"I am not afraid to open a battle front, if necessary," Boldrini was quoted as saying. "Will we give visibility to a group of fanatics? Yes, it's true. But they are not a few, there are thousands and thousands. They are growing every day and they constitute a part of the country that we cannot ignore."

Kyenge, in her comments, thanked her defenders, but refrained from lashing out at her detractors. She stressed that Italy has a long tradition of welcoming foreigners and that that tradition must be appreciated anew and applied in daily life.

"In reality, Italy isn't a racist country," she told reporters. The problem, she said, is ignorance of the "other."

"We need to knock down these walls: Until you know the other, skepticism grows, discrimination grows," she said. "At this point, what is identified as racism has at its base not knowing other cultures. Because in reality, immigration is a richness. Diversity is a resource."

Kyenge, 48, was born in Congo and moved to Italy three decades ago to study medicine. An eye surgeon, she lives in Modena with her Italian husband and two children. She was active in local center-left politics before winning a seat in the lower Chamber of Deputies in February elections, and Premier Enrico Letta brought her into his coalition government last week.

"We hope she will start a new era for Italy, let's hope!" said Kaius Ikejezie, a Nigerian shopping at Rome's Piazza Vittorio market on Friday.

Kyenge has said her priority would be to work to make it easier for children born in Italy to immigrant parents to obtain Italian citizenship. Currently, such children can only apply when they are 18.

"We have people who are born and raised in Italy who don't have an identity," she said. "They don't feel Italian and they don't feel that they belong to their parents' homeland. We need to start from here."

She offered her own experience as an example of the discrimination that confronts non-Italians living here legally and able to contribute to society: Despite having finished at the top of her class in medical school, Kyenge said she couldn't get work in an Italian hospital for two years because she wasn't a citizen.

"I have always fought against any form of discrimination and racism," she said. But she is realistic too of the limitations of her office, the requirements for a "cultural change" and the precariousness of a government made up of longtime political rivals.

"It could be that today I leave the ministry unable to get any results," she said. "But I have to be able to put in place a basis for all those changes that are so longed-for, for all those dreams."

Unlike France, which has had two or more generations of immigrants and several ministers of African origin, Italy is a relative newcomer to immigration. Foreigners made up about 2 percent of Italy's population in 1990; currently the figure stands at 7.5 percent, according to official statistics bureau Istat.

___

Colleen Barry contributed from Milan.

Follow Nicole Winfield at www.twitter.com/nwinfield

Source: http://news.yahoo.com/first-black-italian-minister-seeks-cultural-change-153813881.html

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Shaolin Warrior Stunts Are Even Crazier In Slo-Mo

If you live in a fairly well-populated city you've probably been visited by one of those Shaolin Warrior traveling shows. But the next time they roll through your town you should save your money and instead queue up this fantastic high-speed footage of their incredible acrobatics as captured by BBC Earth Productions.

It goes without saying that you probably shouldn't try any of these stunts at home. Unless you're also a genuine Shaolin Warrior with access to a high-speed camera. Then by all means go ahead and please share your awesome footage in the discussion below.

Source: http://gizmodo.com/shaolin-warrior-stunts-are-even-crazier-in-slo-mo-486995684

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T cells rely on 'rheostat' to help ensure that the immune response matches the threat

T cells rely on 'rheostat' to help ensure that the immune response matches the threat

Wednesday, May 1, 2013

A properly functioning immune system is a lesson in balance, providing protection against disease without attacking healthy tissue. Work led by St. Jude Children's Research Hospital scientists and published recently in Nature Immunology has identified a mechanism that helps T cells find that sweet spot where the strength of the immune response matches the threat.

The finding offers important insight into the immune response. The work also lays the foundation for advancing understanding and treatment of problems that arise when the system malfunctions, including autoimmune disorders that occur when the immune system targets healthy tissue or chronic infectious diseases and cancer where the immune response is insufficient.

T cells are the white blood cells that are the body's warriors, using a variety of weapons to combat cancer and viral infections. The receptors that extend above and below the cell membrane serve as a communication channel enabling the T cell response to match the threat. The researchers found that a component of the T cell receptor functions like a rheostat, helping to regulate a key aspect of that response ? the sometimes explosive production of new T cells called proliferation.

"T cells are a double-edged sword, capable of launching a fierce attack to defeat an infection but also wreaking havoc if the response is too robust and results in damaging healthy tissue," said Dario Vignali, Ph.D., vice chair of the St. Jude Department of Immunology and the paper's senior author. "These findings suggest how T cell receptors help to manage the response and possibly guard against complications resulting from an overly aggressive response."

The results highlight the role of binding regions, called immunoreceptor tyrosine-based activation motifs (ITAMs), in orchestrating an appropriate T cell response. ITAMs are located on the receptor components that extend like tails below the surface of the cell membrane, connecting the T cell receptor to the cell's signaling pathways. Unlike other immune cell types whose receptors have just one or two ITAMs, T cell receptors have 10 ITAMs.

This study suggests that having so many ITAMs gives T cells greater flexibility in responding to threats. The research was published online February 3. Earlier work from Vignali's laboratory showed that mice whose T cells had as few as two working ITAMs could produce cytokines, molecules that combat infection by fueling inflammation. Those T cells, however, could not proliferate.

This study helps to explain why. The new study showed that without a full complement of ITAMs, T cell receptors did not assemble the machinery needed to launch proliferation. That meant proteins named Notch1 and Vav1 did not interact and connect to the T cell receptor. The study showed that these interactions were required to turn on production of another protein, c-Myc, which in turn drives proliferation.

Previous research from the laboratory of Douglas Green, Ph.D., chair of the St. Jude Department of Immunology, showed c-Myc plays a key role in preparing T cells for rapid proliferation. Until this study, however, the steps involved in inducing c-Myc production were unknown.

"Our study shows that Notch1 activation is required for maximal T cell proliferation," Vignali said. The study identified the importance of Notch1 and its association with the T cell receptor, via Vav1, in T cell proliferation. The researchers also showed that fewer functional T cell receptor ITAMs meant less Notch1 was activated.

The perceived strength of the T cell receptor signaling response also affected c-Myc expression in T cells but not cytokine secretion. T cells gauge their response in part by how strongly an antigen binds to the T cell receptor. Antigens are the pieces of the virus or other invader that alert T cells to a problem. A strong bond triggers higher levels of c-Myc and more proliferation. This study showed that T cells with fewer functional ITAMs produced less c-Myc than T cells with their full complement of 10 ITAMs regardless of the strength of the bond.

The findings reflect advances in imaging technology that allowed researchers to detect molecular interactions at the nanoscale level, said the paper's first author Clifford Guy, Ph.D., a postdoctoral fellow in Vignali's laboratory. A nanometer is one trillionth of a meter. The technology used in this study meant scientists could track how the number of functional ITAMs affected the ability of Vav1 and Notch1 to interact to within 30 to 50 nanometers, less than one-quarter the width of a human hair.

"This suggests that much like a rheostat controls the intensity of a lamp, ITAMs regulate how T cells respond to external threats, allowing them to scale the size of the response according to the size of the perceived threat," Guy said.

###

St. Jude Children's Research Hospital: http://www.stjude.org

Thanks to St. Jude Children's Research Hospital for this article.

This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.

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Book News: Amazon in the Arab World, Playing Moby : The New ...

Twenty-five handwritten manuscripts, including those of ?The Great Gatsby,? ?The Adventures of Huckleberry Finn,? and ?Mrs. Dalloway.?

Does a poem that Sylvia Plath wrote two weeks before her death reveal her as being ?disturbed??

Michael Bhaskar explores the reasons for Amazon?s reluctance to enter the Arab book world.

?A sealed letter arrived at the palace?s library, leaving staff stunned. The letter, written by a former Lambeth Palace Library employee before his death, revealed the whereabouts of many of the library?s precious books.? Fourteen hundred stolen books were recently recovered by London?s Lambeth Palace Library.

Read this Q. & A. with the makers of Moby Dick, the video game.

Source: http://www.newyorker.com/online/blogs/books/2013/05/book-news-amazon-in-arab-world-playing-moby.html

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Russia had elder Boston suspect under surveillance

In this undated photo provided by the Dagestani branch of the Federal Security Service William Plotnikov, right, poses for a photo. Security officials suspected ties between elder Boston bombing suspect Tamerlan Tsarnaev and the Canadian, an ethnic Russian named William Plotnikov, who had joined the Islamic insurgency in the region. Russian agents placed the elder Boston bombing suspect under surveillance during a six-month visit to southern Russia last year, then scrambled to find him when he suddenly disappeared after police killed a Canadian jihadist, a security official told The Associated Press. (AP Photo/Dagestani branch of the Federal Security Service via NewsTeam)

In this undated photo provided by the Dagestani branch of the Federal Security Service William Plotnikov, right, poses for a photo. Security officials suspected ties between elder Boston bombing suspect Tamerlan Tsarnaev and the Canadian, an ethnic Russian named William Plotnikov, who had joined the Islamic insurgency in the region. Russian agents placed the elder Boston bombing suspect under surveillance during a six-month visit to southern Russia last year, then scrambled to find him when he suddenly disappeared after police killed a Canadian jihadist, a security official told The Associated Press. (AP Photo/Dagestani branch of the Federal Security Service via NewsTeam)

EDS NOTE: GRAPHIC CONTENT In this undated photo provided by the Dagestani branch of the Federal Security Service, the body of William Plotnikov, killed in a standoff with police in Dagestan. Security officials suspected ties between elder Boston bombing suspect Tamerlan Tsarnaev and the Canadian, an ethnic Russian named William Plotnikov, who had joined the Islamic insurgency in the region. Russian agents placed Tsarnaev under surveillance during a six-month visit to southern Russia last year, then scrambled to find him when he suddenly disappeared after police killed a Canadian jihadist, a security official told The Associated Press. (AP Photo/Dagestani branch of the Federal Security Service via NewsTeam)

MAKHACHKALA, Russia (AP) ? Russian agents placed the elder Boston bombing suspect under surveillance during a six-month visit to southern Russia last year, then scrambled to find him when he suddenly disappeared after police killed a Canadian jihadist, a security official told The Associated Press.

U.S. law enforcement officials have been trying to determine whether Tamerlan Tsarnaev was indoctrinated or trained by militants during his visit to Dagestan, a Caspian Sea province that has become the center of a simmering Islamic insurgency.

The security official with the Anti-Extremism Center, a federal agency under Russia's Interior Ministry, confirmed the Russians shared their concerns. He told the AP that Russian agents were watching Tsarnaev, and that they searched for him when he disappeared two days after the July 2012 death of the Canadian man, who had joined the Islamic insurgency in the region. The official spoke only on condition of anonymity because he was not authorized to speak to the news media.

Security officials suspected ties between Tsarnaev and the Canadian ? an ethnic Russian named William Plotnikov ? according to the Novaya Gazeta newspaper, which is known for its independence and investigative reporting and cited an unnamed official with the Anti-Extremism Center, which tracks militants. The newspaper said the men had social networking ties that brought Tsarnaev to the attention of Russian security services for the first time in late 2010.

It certainly wouldn't be surprising if the men had met. Both were amateur boxers of roughly the same age whose families had moved from Russia to North America when they were teenagers. In recent years, both had turned to Islam and expressed radical beliefs. And both had traveled to Dagestan, a republic of some 3 million people.

The AP could not independently confirm whether the two men had communicated on social networks or crossed paths either in Dagestan or in Toronto, where Plotnikov had lived with his parents and where Tsarnaev had an aunt.

After Plotnikov was killed, Tsarnaev left suddenly for the U.S., not waiting to pick up his new Russian passport ? ostensibly one of his main reasons for coming to Russia. The official said his sudden departure was considered suspicious.

Plotnikov's father told the Canadian network CBCNews on Monday that his son had broken off contact when he returned to Russia in 2010 and he had no way of knowing whether his son knew Tsarnaev.

In an August interview with the Canadian newspaper National Post, Vitaly Plotnikov said his son, who was 23 when he died, had converted to Islam in 2009 and quickly became radicalized. But he said he fully understood what his son was up to in Russia only when he received photographs and videos after his death.

In one photo, a smiling William Plotnikov is shown posing in the woods, an automatic rifle slung over his shoulder and a camouflage ammunition belt around his waist. In the videos, which the National Post reporter watched with the father, the younger Plotnikov talked openly of planning to kill in the name of Allah.

Plotnikov had been detained in Dagestan in December 2010 on suspicion of having ties to the militants and during his interrogation was forced to hand over a list of social networking friends from the United States and Canada who like him had once lived in Russia, Novaya Gazeta reported.

The newspaper said Tsarnaev's name was on that list, bringing him for the first time to the attention of Russia's secret services.

Novaya Gazeta, which is part-owned by former Soviet President Mikhail Gorbachev and wealthy businessman Alexander Lebedev, has regularly criticized the Kremlin. One of its best known reporters, Anna Politkovskaya, angered the Kremlin with her reporting from Chechnya, and her 2006 murder in a Moscow elevator was widely presumed to have been in connection with her journalistic work.

The Islamic insurgency in Dagestan grew out of the fierce fighting between Russian troops and separatists in neighboring Chechnya that raged in the 1990s. Attacks now are carried out almost daily in Dagestan against police and security forces, who respond with special operations of their own to wipe out the militants.

As recently as Sunday, two suspected militants were killed in a shootout after being cornered in a house in the Dagestani village of Chontaul, according to police spokeswoman Fatina Ubaidatova.

Plotnikov was among seven suspected militants killed on July 14 during a standoff with police in the Dagestani village of Utamysh, according to the official police record.

After Plotnikov's death, Russian security agents lost track of Tsarnaev and went to see his father in Makhachkala, the capital of Dagestan, who told them that his son had returned to the U.S., Novaya Gazeta said.

The agents did not believe the father, since Tsarnaev had left without picking up his new Russian passport, and they continued to search for him, the newspaper reported.

The Russians later determined that Tsarnaev had flown to Moscow on July 16 and to the United States the following day, the newspaper said. Tsarnaev arrived in New York on July 17.

Russian migration officials have said they were puzzled that Tsarnaev applied for the passport but left before it was ready.

His father, Anzhor Tsarnaev, said last week that his elder son stayed with him while waiting for the passport to be processed. He could not be reached Tuesday for comment on the Novaya Gazeta report.

The Tsarnaev family had lived briefly in Dagestan before moving to the United States a decade ago. Both parents returned to Dagestan last year.

The official with Russia's Anti-Extremism Center said Tsarnaev was filmed attending a mosque in Makhachkala whose worshippers adhere to a more radical strain of Islam. The official would give no further details about what the Russian security services knew about Tsarnaev's activities in Dagestan or about any possible connection to Plotnikov.

The AP was unable to determine whether the official was the same one who provided the information to Novaya Gazeta.

Plotnikov had settled in Utamysh, a small village about 70 kilometers (40 miles) from Makhachkala. It was not known whether he had spent any significant amount of time in Dagestan's capital.

Novaya Gazeta said Tsarnaev was also seen in the company of Mahmud Nidal ? a man who was both Palestinian and Kumyk, one of the dozens of ethnic groups living in Dagestan ? and who was believed to have ties to Islamic militants in the southern Russian region.

Nidal was killed in May 2012 after refusing to give himself up to security forces that had surrounded a house in Makhachkala, according to official police records.

Shortly after Plotnikov identified Tsarnaev during his December 2010 interrogation, the Russian secret services, the FSB, studied Tsarnaev's pages on social networking sites and asked the FBI for more information, the Russian newspaper said.

The FBI has acknowledged receiving the request. The U.S. agency said it opened an investigation, but when no evidence of terrorism was found and no further information from the Russians was forthcoming, the case was closed in June 2011.

___

Berry reported from Moscow.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/cae69a7523db45408eeb2b3a98c0c9c5/Article_2013-04-30-Russia-Boston%20Suspect/id-d4755565fc4147eeae6b70b904c54a20

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Intel details 4th-gen Core's HD 5000, Iris and Iris Pro graphics: up to 3X faster, 3-display collage mode

Many already believe that the real highlight of Intel's 4th-generation Core processor lineup would be a giant graphics update. Today, Intel is revealing that they're right -- and, importantly, that there's an equally large shift in naming strategy. Where 3rd-generation Core graphics were divided into two tiers, the new generation is focused on three, two of which are built for performance over efficiency. Ultrabooks with 15W U-series processors will use comparatively ordinary (if still faster) HD 5000 graphics. Thin-and-light laptops with 28W U-series chips get a new tier, Iris, that Intel claims is up to twice as fast in 3D as last year's HD Graphics. Power-hungry parts see even more of a boost: they can carry Iris Pro graphics with embedded DRAM, which should double the 3D speed on H-series mobile chips (47-55W of typical power) and triple it for the R-series (around 65-84W) on the desktop. We also know that M-series laptop and K-series desktop CPUs will have Iris Pro options.

The feature set for the graphics trio is slightly more familiar to us, although there are a few tricks up Intel's sleeve. All three can draw DirectX 11.1 and OpenGL 4 visuals, as well as take on OpenCL 1.2 computing and faster media processing. We're almost more interested in the display modes, though. Along with receiving "enhanced" 4K output, the new Core graphics can handle a 3-screen collage mode -- we won't need dedicated video for a large, multi-monitor canvas. Sadly, Intel isn't providing more than incidental details about the processors themselves, although it has already teased that we'll get the full story around the Computex show in early June.

Gallery: Intel HD 5000, Iris and Iris Pro graphics details

Filed under: Desktops, Laptops, Intel

Comments

Source: Intel

Source: http://feeds.engadget.com/~r/weblogsinc/engadget/~3/ToHKGEFHNmE/

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Endometrial and acute myeloid leukemia cancer genomes characterized

May 1, 2013 ? Two studies from The Cancer Genome Atlas (TCGA) program reveal details about the genomic landscapes of acute myeloid leukemia (AML) and endometrial cancer. Both provide new insights into the molecular underpinnings of these cancers with the potential to improve treatment. These studies represent the sixth and seventh in a series of genomes of at least 20 major cancers.

The first study is on endometrial cancer. The study establishes basis for genomic classification of endometrial cancers; proper categorization is important for choosing the best treatment.

A comprehensive genomic analysis of nearly 400 endometrial tumors suggests that certain molecular characteristics -- such as the frequency of mutations -- could complement current pathology methods and help distinguish between principal types of endometrial tumors, as well as provide insights into potential treatment strategies. In addition, the study, led by investigators in The Cancer Genome Atlas (TCGA) Research Network, revealed four novel tumor subtypes, while also identifying genomic similarities between endometrial and other types of cancers, including breast, ovarian, and colorectal cancers.

These findings represent the most comprehensive characterization of the molecular alterations in endometrial cancers available to date. They were published May 2, 2013, in the journal Nature. TCGA is funded and managed by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI), both part of the National Institutes of Health.

"With this latest study in a series of 20 planned TCGA tumor type characterizations, more genomic similarities are emerging between disparate tumor types," said NIH Director Francis S. Collins, M.D., Ph.D. "Teasing out heretofore unknown genomic markers or mutations in various cancers is again proving the value of TCGA."

Depiction of female reproductive system with endometrium

Clinically, endometrial cancers fall into two categories: endometrioid (type I) and serous (type II) tumors. Type I is correlated with excess estrogen, obesity, and a favorable prognosis, while type II is more common in older women and generally has a less favorable outcome. Type I tumors are often treated with radiation therapy, which helps stop or slow cancer growth, given in addition to or after the primary treatment. Type II tumors are generally treated with chemotherapy, in which drugs are used to kill the cancer cells or stop them from growing.

Distinguishing between different types of endometrial cancers is currently based on histology, an examination of a thin slice of tissue under a microscope. But categorizing endometrial cancer tissues is often difficult, and specialists frequently disagree on the classification of individual cases.

In this study, investigators showed that approximately 25 percent of tumors that pathologists classified as high-grade endometrioid showed frequent mutations in TP53, a tumor suppressor gene, as well as extensive copy number alterations, a term for when a cell has too many or too few copies of a genomic segment. Both are key molecular characteristics associated with serous tumors, along with a small number of DNA methylation changes, which are additions of a basic chemical unit to pieces of DNA. Most endometrioid tumors, by contrast, have few copy number alterations or mutations in TP53, though there are frequent mutations in other well known cancer-associated genes, including PTEN, another tumor suppressor gene, and KRAS, a gene involved in regulating cell division.

These data suggest that some high grade endometrioid tumors have developed a strikingly similar pattern of alterations to serous tumors, and may benefit from a similar course of treatment.

"This study highlights the fact that some tumors with the same characterization by pathologists may have very different molecular features. That's where these findings will be directly implemented in additional research, and also in the context of clinical trials," said Douglas A. Levine, M.D., head of the Gynecology Research Laboratory at Memorial Sloan-Kettering Cancer Center, New York, and a co-leader in the study.

According to the authors, the new findings provide a roadmap for future clinical trials for endometrial cancer. "Each tumor subtype might warrant dedicated clinical trials because of the marked genomic differences between them that are indicative of different drivers of cancer," said study co-leader Elaine Mardis, Ph.D., co-director of the Genome Institute at Washington University School of Medicine, St. Louis. "Developing therapies for each subtype independent of the other may improve outcomes, as has been shown in breast cancer."

Investigators also found genomic similarities between endometrial cancers and other tumor types. Previous TCGA research showed that a form of ovarian cancer (high-grade serous ovarian carcinoma) and a subtype of breast cancer (basal-like breast cancer) share many genomic features. In this study, the scientists found that endometrial serous carcinoma also has some of these same genomic characteristics. The cancers share a high frequency of mutations in TP53 (between 84 and 96 percent) and a low frequency in PTEN, with only 1 to 2 percent mutated. Surprisingly, the researchers also found many shared characteristics between endometrioid tumors and colorectal tumors. Both cancer types demonstrate a high frequency of microsatellite instability, where the repair mechanism for DNA is broken, and mutations in POLE, a gene responsible for producing a protein involved in DNA replication and repair. These genomic changes led to high mutation rates in both tumor types.

"TCGA's multidimensional approach to collecting genomic data, including clinical and pathology information, have made these findings possible," said Harold Varmus, M.D., NCI director. "Without the integrated characterization of so many tumor samples, correlations between histology and genomic data may not have been observed or potential clinical outcomes identified."

With a complete analysis of the study's findings, investigators have identified four novel genomic-based subtypes of endometrial cancer, which may set the stage for new diagnostic and treatment approaches. Each of the four genomic subtypes clustered together and was named for one of its notable characteristics:

• The POLE ultramutated group was named for its unusually high mutation rates and hotspot mutations (sequences highly susceptible to mutation) in the POLE gene.
• The hypermutated microsatellite instability group exhibited a high mutation rate, as well as few copy number alterations, but did not carry mutations in the POLE gene.
• The copy number low group showed the greatest microsatellite stability but a high frequency of mutations in CTNNB1, a gene critical for maintaining the linings of organs, such as the endometrium.
• The copy number high subtype was composed of mostly serous tumors, but included some endometrioid samples. This subtype displayed copy number alterations and a mutation landscape that was characteristic of serous tumors.

Endometrial cancer is the fourth most commonly diagnosed cancer among women in the United States. NCI estimates that close to 50,000 women will be diagnosed with endometrial cancer in 2013, with more than an estimated 8,000 deaths from the disease. For a majority of patients diagnosed with aggressive, high grade tumors with metastases, the five-year survival rate is about 16 percent, though chemotherapy has been associated with an improvement in survival, and new targeted agents are being tested.

"Finding genomic similarities among types of breast, ovarian, endometrial and colorectal tumors once again reveals that cancer, although very complex, may have themes extending beyond tissue type that can be exploited for therapeutic benefit," said Eric D. Green, M.D., Ph.D., NHGRI director. "These similar genomic features demonstrate hitherto unknown commonalities among these cancers.

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The above story is reprinted from materials provided by NIH/National Cancer Institute.

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Journal Reference:

1. Gad Getz et al. Integrated genomic characterization of endometrial carcinoma. Nature, 2013; 497 (7447): 67 DOI: 10.1038/nature12113

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Source: http://feeds.sciencedaily.com/~r/sciencedaily/health_medicine/genes/~3/bAEjDvRPM2A/130501154438.htm

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