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Public release date: 1-May-2013[ | E-mail |
Share ] Contact: Marjorie Montemayor-Quellenberg
mmontemayor-quellenberg@partners.org
617-534-2208
Brigham and Women's Hospital
Cancer Genome Atlas Research Network discovers mutations that may affect treatment of patients with endometrial cancer
Boston, MA A study from the Cancer Genome Atlas Research Network, led by the National Cancer Institute and the National Human Genome Research Institute, report that mutations discovered in endometrial cancer genes may directly impact treatment plans for women with aggressive endometrial cancer, as well as the classification of endometrial cancer tumors.
The study will be published in the May 2, 2013 issue of Nature.
The researchers performed an integrated analysis of endometrial cancer tumor samples from 373 patients using array- and sequencing-based technologies. Among their findings, two endometrial cancer tumor subtypesuterine serous tumors and high-grade endometrioid tumorsshared several genetic mutations.
The researchers found that approximately 25 percent of tumors classified as high-grade endometrioid actually had genetic features similar to uterine serous carcinoma tumors, such as extensive copy number alterations and frequent mutations in the TP53 gene. The TP53 gene encodes for a tumor suppressor protein called p53. Moreover, uterine serous carcinomas shared genomic features with ovarian serous and basal-like breast carcinomas.
Early stage endometrioid tumors are often treated with adjuvant radiotherapy, while similarly staged serous tumors are treated with chemotherapy. Based on these compelling genetic similarities, the researchers note that clinicians should carefully consider treating copy number-altered endometrioid patients with chemotherapy rather than adjuvant radiotherapy and formally test such hypotheses in prospective clinical trials.
"Some of the results reported in this paper can change the way endometrial cancers are classified and provide opportunities to test new treatment protocols for patients with this cancer," said Raju S. Kucherlapati, PhD, Paul C. Cabot Professor of Genetics and Professor of Medicine at Brigham and Women's Hospital, and study author.
Further analysis and characterization of endometrial tumor subtypes also led the researchers to suggest a reclassification of endometrial cancers into four categories, as opposed to the current broad classification of two categories. The four categories are: POLE ultramutated, microsatellite instability hypermutated, copy number low, and copy number high.
"These findings suggest that a subset of endometrial tumors have distinct patterns of copy number alterations and mutations that do not correlate with traditional grade or make-up of tumor tissue," said Kucherlapati. The Genome Characterization Center in The Cancer Genome Atlas headed by Kucherlapati conducted whole genome sequencing of the tumors and identified copy number variations and structural rearrangements in these tumors.
Endometrial cancer occurs in the lining of the uterus, and is the fourth most common malignancy among women in the United States, with an estimated 47,000 new cases and 8,000 deaths in 2012.
###
The Cancer Genome Atlas Research Network is a project led by the National Cancer Institute and the National Human Genome Research Institute. Its mission is to catalogue genetic mutations responsible for cancer, as well as utilize the latest genomic technologies to improve the ability to diagnose, treat and prevent cancer through a better understanding of the genetic basis of disease.
This research was supported by the National Institutes of Health (5U24CA143799-04, 5U24CA143835-04, 5U24CA143840-04, 5U24CA143843-04, 5U24CA143845-04, 5U24CA143848-04, 5U24CA143858-04, 5U24CA143866-04, 5U24CA143867-04, 5U24CA143882-04, 5U24CA143883-04, 5U24CA144025-04, U54HG003067, U54HG003079, and U54HG003273).
Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. BWH has more than 3.5 million annual patient visits, is the largest birthing center in New England and employs more than 15,000 people. The Brigham's medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, involving nearly 1,000 physician-investigators and renowned biomedical scientists and faculty supported by nearly $625 million in funding. BWH continually pushes the boundaries of medicine, including building on its legacy in organ transplantation by performing the first face transplants in the U.S. in 2011. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies, OurGenes and the Women's Health Initiative. For more information and resources, please visit BWH's online newsroom.
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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Public release date: 1-May-2013[ | E-mail |
Share ] Contact: Marjorie Montemayor-Quellenberg
mmontemayor-quellenberg@partners.org
617-534-2208
Brigham and Women's Hospital
Cancer Genome Atlas Research Network discovers mutations that may affect treatment of patients with endometrial cancer
Boston, MA A study from the Cancer Genome Atlas Research Network, led by the National Cancer Institute and the National Human Genome Research Institute, report that mutations discovered in endometrial cancer genes may directly impact treatment plans for women with aggressive endometrial cancer, as well as the classification of endometrial cancer tumors.
The study will be published in the May 2, 2013 issue of Nature.
The researchers performed an integrated analysis of endometrial cancer tumor samples from 373 patients using array- and sequencing-based technologies. Among their findings, two endometrial cancer tumor subtypesuterine serous tumors and high-grade endometrioid tumorsshared several genetic mutations.
The researchers found that approximately 25 percent of tumors classified as high-grade endometrioid actually had genetic features similar to uterine serous carcinoma tumors, such as extensive copy number alterations and frequent mutations in the TP53 gene. The TP53 gene encodes for a tumor suppressor protein called p53. Moreover, uterine serous carcinomas shared genomic features with ovarian serous and basal-like breast carcinomas.
Early stage endometrioid tumors are often treated with adjuvant radiotherapy, while similarly staged serous tumors are treated with chemotherapy. Based on these compelling genetic similarities, the researchers note that clinicians should carefully consider treating copy number-altered endometrioid patients with chemotherapy rather than adjuvant radiotherapy and formally test such hypotheses in prospective clinical trials.
"Some of the results reported in this paper can change the way endometrial cancers are classified and provide opportunities to test new treatment protocols for patients with this cancer," said Raju S. Kucherlapati, PhD, Paul C. Cabot Professor of Genetics and Professor of Medicine at Brigham and Women's Hospital, and study author.
Further analysis and characterization of endometrial tumor subtypes also led the researchers to suggest a reclassification of endometrial cancers into four categories, as opposed to the current broad classification of two categories. The four categories are: POLE ultramutated, microsatellite instability hypermutated, copy number low, and copy number high.
"These findings suggest that a subset of endometrial tumors have distinct patterns of copy number alterations and mutations that do not correlate with traditional grade or make-up of tumor tissue," said Kucherlapati. The Genome Characterization Center in The Cancer Genome Atlas headed by Kucherlapati conducted whole genome sequencing of the tumors and identified copy number variations and structural rearrangements in these tumors.
Endometrial cancer occurs in the lining of the uterus, and is the fourth most common malignancy among women in the United States, with an estimated 47,000 new cases and 8,000 deaths in 2012.
###
The Cancer Genome Atlas Research Network is a project led by the National Cancer Institute and the National Human Genome Research Institute. Its mission is to catalogue genetic mutations responsible for cancer, as well as utilize the latest genomic technologies to improve the ability to diagnose, treat and prevent cancer through a better understanding of the genetic basis of disease.
This research was supported by the National Institutes of Health (5U24CA143799-04, 5U24CA143835-04, 5U24CA143840-04, 5U24CA143843-04, 5U24CA143845-04, 5U24CA143848-04, 5U24CA143858-04, 5U24CA143866-04, 5U24CA143867-04, 5U24CA143882-04, 5U24CA143883-04, 5U24CA144025-04, U54HG003067, U54HG003079, and U54HG003273).
Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. BWH has more than 3.5 million annual patient visits, is the largest birthing center in New England and employs more than 15,000 people. The Brigham's medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, involving nearly 1,000 physician-investigators and renowned biomedical scientists and faculty supported by nearly $625 million in funding. BWH continually pushes the boundaries of medicine, including building on its legacy in organ transplantation by performing the first face transplants in the U.S. in 2011. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies, OurGenes and the Women's Health Initiative. For more information and resources, please visit BWH's online newsroom.
[ | E-mail | Share ] ?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Source: http://www.eurekalert.org/pub_releases/2013-05/bawh-aps042913.php
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