المؤلفون: Makohon-Moore, Alvin P, Zhang, Ming, Reiter, Johannes G, Bozic, Ivana, Allen, Benjamin, Kundu, Deepanjan, Chatterjee, Krishnendu, Wong, Fay, Jiao, Yuchen, Kohutek, Zachary A, Hong, Jungeui, Attiyeh, Marc, Javier, Breanna, Wood, Laura D, Hruban, Ralph H, Nowak, Martin A, Papadopoulos, Nickolas, Kinzler, Kenneth W, Vogelstein, Bert, Iacobuzio-Donahue, Christine A

المصدر: Nature Genetics; March 2017, Vol. 49 Issue: 3 p358-366, 9p

مستخلص: The extent of heterogeneity among driver gene mutations present in naturally occurring metastases—that is, treatment-naive metastatic disease—is largely unknown. To address this issue, we carried out 60× whole-genome sequencing of 26 metastases from four patients with pancreatic cancer. We found that identical mutations in known driver genes were present in every metastatic lesion for each patient studied. Passenger gene mutations, which do not have known or predicted functional consequences, accounted for all intratumoral heterogeneity. Even with respect to these passenger mutations, our analysis suggests that the genetic similarity among the founding cells of metastases was higher than that expected for any two cells randomly taken from a normal tissue. The uniformity of known driver gene mutations among metastases in the same patient has critical and encouraging implications for the success of future targeted therapies in advanced-stage disease.

المؤلفون: Zhang, Ming, Wang, Yuxuan, McMahon, Kevin, Wang, Qing, Kinzler, Kenneth W, Papadopoulos, Nickolas, Vogelstein, Bert, Jones, Sian, Sausen, Mark, Sharma, Rajni, Wood, Laura D, Montgomery, Elizabeth A, Hruban, Ralph H, Belzberg, Allan J, Chaichana, Kaisorn, Gallia, Gary L, Gokaslan, Ziya L, Riggins, Greg J, Wolinksy, Jean-Paul, Bettegowda, Chetan

المصدر: Nature Genetics; Nov2014, Vol. 46 Issue 11, p1170-1172, 3p

مصطلحات موضوعية: NEUROFIBROMA, SOMATIC mutation, NEUROFIBROMATOSIS 1, GENETIC code, PERIPHERAL nervous system, TUMOR suppressor genes

مستخلص: Neurofibromatosis 1 is a hereditary syndrome characterized by the development of numerous benign neurofibromas, a small subset of which progress to malignant peripheral nerve sheath tumors (MPNSTs). To better understand the genetic basis for MPNSTs, we performed genome-wide or targeted sequencing on 50 cases. Sixteen MPNSTs but none of the neurofibromas tested were found to have somatic mutations in SUZ12, implicating it as having a central role in malignant transformation. [ABSTRACT FROM AUTHOR]

: Copyright of Nature Genetics is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Li, Meng, Zhao, Hong, Zhang, Xiaosong, Wood, Laura D., Anders, Robert A., Choti, Michael A., Pawlik, Timothy M., Daniel, Hubert D., Kannangai, Rajesh, Offerhaus, G Johan A., Velculescu, Victor E., Wang, Linfang, Zhou, Shibin, Vogelstein, Bert, Hruban, Ralph H, Papadopoulos, Nick, Cai, Jianqiang, Torbenson, Michael S., Kinzler, Kenneth W.

المصدر: Nature Genetics; Sep2011, Vol. 43 Issue 9, p828-829, 2p, 2 Charts

مصطلحات موضوعية: CHROMATIN, LIVER cancer, NUCLEOTIDE sequence, HEPATITIS C virus, GENETIC mutation, HEPATITIS B virus, GENETICS

مصطلحات جغرافية: UNITED States, EUROPE

مستخلص: Through exomic sequencing of ten hepatitis C virus (HCV)-associated hepatocellular carcinomas (HCC) and subsequent evaluation of additional affected individuals, we discovered novel inactivating mutations of ARID2 in four major subtypes of HCC (HCV-associated HCC, hepatitis B virus (HBV)-associated HCC, alcohol-associated HCC and HCC with no known etiology). Notably, 18.2% of individuals with HCV-associated HCC in the United States and Europe harbored ARID2 inactivation mutations, suggesting that ARID2 is a tumor suppressor gene that is relatively commonly mutated in this tumor subtype. [ABSTRACT FROM AUTHOR]

: Copyright of Nature Genetics is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)