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June 01, 2013

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DNA similarities increasingly seen in different cancers

May 1, 2013
Courtesy of the National Cancer Institute
and World Science staff

A large study of en­do­me­trial can­cer has made it in­creas­ingly ap­par­ent that can­cers of dif­fer­ent or­gans some­times share ge­net­ic com­monal­i­ties, re­search­ers sug­gest.

The ge­no­mic anal­y­sis of nearly 400 en­do­me­trial tu­mors is serv­ing as a hint to some sci­en­tists that newer treat­ment ap­proaches could ex­ploit these si­m­i­lar­i­ties to bet­ter tar­get tu­mors by type.

The study identified four new sub­types of en­do­me­trial tu­mors, which form in the lin­ing of the uter­us. It al­so found cer­tain ge­net­ic si­m­i­lar­i­ties among en­do­me­trial and can­cers in­clud­ing breast, ovar­i­an, and col­orec­tal can­cers.

The find­ings, de­scribed as the fullest de­scrip­tion of the mo­lec­u­lar al­tera­t­ions in en­do­me­trial can­cers avail­a­ble, ap­pear in the May 2 is­sue of the jour­nal Na­ture. Sci­en­tists in a col­la­bora­t­ion called The Can­cer Ge­nome At­las, or TCGA, Re­search Net­work led the proj­ect.

“More ge­no­mic si­m­i­lar­i­ties are emerg­ing be­tween dis­par­ate tu­mor types,” said Fran­cis S. Col­lins, di­rec­tor of the U.S. Na­t­ional In­sti­tutes of Health, two parts of which funded and man­aged the stu­dy: the Na­t­ional Can­cer In­sti­tute and the Na­t­ional Hu­man Ge­nome Re­search In­sti­tute. 

A ge­nome is the full set of genes in an or­gan­ism. When re­search­ers speak of can­cer ge­no­mics, they mean the study of genes in can­cer cells, where the DNA code is cor­rupted.

En­do­me­trial can­cers fall in­to two bas­ic types: “en­dometri­oid” and “se­rous” tu­mors, which are gen­er­ally a worse prob­lem. Doc­tors cur­rently tell apart the types us­ing a mi­cro­scope, but this pro­cess is dif­fi­cult and error-prone. In the stu­dy, in­ves­ti­ga­tors found that about a fourth of tu­mors that pathol­o­gists had clas­si­fied as “high-grade en­dometri­oid” in this way showed strik­ingly si­m­i­lar pat­tern of muta­t­ions to se­rous tu­mors, sug­gesting they might ben­e­fit from si­m­i­lar treat­ment.

The new find­ings pro­vide a roadmap for fu­ture clin­i­cal tri­als for en­do­me­trial can­cer, the au­thors said. “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, 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 had found that a form of ovar­i­an can­cer called high-grade se­rous ovar­i­an car­ci­no­ma, and a sub­type of breast can­cer called basal-like breast can­cer, share many ge­no­mic fea­tures. In the new work, the sci­en­tists found that en­do­me­trial se­rous tumors have some of these same prop­erties.

“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,” added Er­ic D. Green, the Na­t­ional Hu­man Ge­nome Re­search In­sti­tute di­rec­tor. “These si­m­i­lar ge­no­mic fea­tures dem­on­strate hith­er­to un­known com­monal­i­ties among these can­cers.”

En­do­me­trial can­cer is the fourth most com­monly di­ag­nosed can­cer among wom­en in the Un­ited States. The Na­t­ional Can­cer In­sti­tute 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 drugs are un­der stu­dy.


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A huge new study of endometrial cancer has made it increasingly apparent that cancers of different organs sometimes share genetic commonalities, researchers suggest. The genomic analysis of nearly 400 endometrial tumors is serving as a hint to some scientists that newer treatment approaches could exploit these similarities to better target tumors by type. The study revealed four new subtypes of endometrial tumors, which form in the lining of the uterus. The study also found certain genetic similarities among endometrial and cancers including breast, ovarian, and colorectal cancers. The findings, described as the fullest description of the molecular alterations in endometrial cancers available, were published May 2 in the journal Nature. Scientists in a collaboration called The Cancer Genome Atlas, or TCGA, Research Network led the project. “More genomic similarities are emerging between disparate tumor types,” said Francis S. Collins, director of the U.S. National Institutes of Health, two parts of which funded and managed the study: the National Cancer Institute and the National Human Genome Research Institute. A genome is the full set of genes in an organism. When researchers speak of cancer genomics, they mean the study of genes in cancer cells, in which the DNA code is corrupted. Endometrial cancers fall into two basic types: “endometrioid” and “serous” tumors, which are generally a worse problem. Doctors currently tell apart the types using a microscope, but this process is difficult and error-prone. In the study, investigators found that about a fourth of tumors that pathologists had classified as “high-grade endometrioid” in this way showed strikingly similar pattern of mutations to serous tumors, suggesting they might benefit from similar treatment. The new findings provide a roadmap for future clinical trials for endometrial cancer, the authors said. “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, 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 had found that a form of ovarian cancer called high-grade serous ovarian carcinoma, and a subtype of breast cancer called basal-like breast cancer, share many genomic features. In the new work, the scientists found that endometrial serous carcinoma also has some of these same characteristics. “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,” added Eric D. Green, the National Human Genome Research Institute director. “These similar genomic features demonstrate hitherto unknown commonalities among these cancers.” Endometrial cancer is the fourth most commonly diagnosed cancer among women in the United States. The National Cancer Institute 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 drugs are under study.