Whole-exome sequencing uncovers frequent GNAS mutations in intraductal papillary mucinous neoplasms of the pancreas.
Whole-exome sequencing uncovers frequent GNAS mutations in intraductal papillary mucinous neoplasms of the pancreas.
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DOI：
10.1038/srep00161
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发表时间：
2011
影响因子：
4.6
通讯作者：
Shiratori, Keiko
中科院分区：
文献类型：
--
作者：
Furukawa, Toru;Kuboki, Yuko;Tanji, Etsuko;Yoshida, Shoko;Hatori, Takashi;Yamamoto, Masakazu;Shibata, Noriyuki;Shimizu, Kyoko;Kamatani, Naoyuki;Shiratori, Keiko
导管内乳头状粘液瘤（IPMN）是一种常见的胰腺囊性肿瘤，常具有侵袭性和转移性，预后较差。已知IPMN特有的分子改变很少。我们对一个原发性IPMN组织进行了全外显子组测序，发现了KCNF1、DYNC1H1、PGCP、STAB1、PTPRM、PRPF8、RNASE3、SPHKAP、MLXIPL、VPS13C、PRCC、GNAS、KRAS、RBM10、RNF43、DOCK2和CENPF的体细胞突变。我们进一步分析了118例ipmn和32例胰腺导管腺癌（pda）的GNAS突变，结果显示118例ipmn中有48例（40.7%）存在GNAS突变，而32例pda中没有GNAS突变。由GNAS编码的g蛋白α亚基及其下游靶点蛋白激酶A磷酸化底物在IPMN中明显表达；后者与肿瘤分级有关。这些结果表明，GNAS突变是IPMN的常见和特异性突变，g蛋白信号的激活似乎在IPMN中起关键作用。
Intraductal papillary mucinous neoplasm (IPMN) is a common pancreatic cystic neoplasm that is often invasive and metastatic, resulting in a poor prognosis. Few molecular alterations unique to IPMN are known. We performed whole-exome sequencing for a primary IPMN tissue, which uncovered somatic mutations in KCNF1, DYNC1H1, PGCP, STAB1, PTPRM, PRPF8, RNASE3, SPHKAP, MLXIPL, VPS13C, PRCC, GNAS, KRAS, RBM10, RNF43, DOCK2, and CENPF. We further analyzed GNAS mutations in archival cases of 118 IPMNs and 32 pancreatic ductal adenocarcinomas (PDAs), which revealed that 48 (40.7%) of the 118 IPMNs but none of the 32 PDAs harbored GNAS mutations. G-protein alpha-subunit encoded by GNAS and its downstream targets, phosphorylated substrates of protein kinase A, were evidently expressed in IPMN; the latter was associated with neoplastic grade. These results indicate that GNAS mutations are common and specific for IPMN, and activation of G-protein signaling appears to play a pivotal role in IPMN.
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胰腺神经内分泌肿瘤中经常改变DAXX/ATRX，MEN1和MTOR途径基因。
DOI：
10.1126/science.1200609
发表时间：
2011-03-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Jiao Y;Shi C;Edil BH;de Wilde RF;Klimstra DS;Maitra A;Schulick RD;Tang LH;Wolfgang CL;Choti MA;Velculescu VE;Diaz LA Jr;Vogelstein B;Kinzler KW;Hruban RH;Papadopoulos N
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Papadopoulos N
DOI：
10.1126/science.1164382
发表时间：
2008-09-26
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
Parsons DW;Jones S;Zhang X;Lin JC;Leary RJ;Angenendt P;Mankoo P;Carter H;Siu IM;Gallia GL;Olivi A;McLendon R;Rasheed BA;Keir S;Nikolskaya T;Nikolsky Y;Busam DA;Tekleab H;Diaz LA Jr;Hartigan J;Smith DR;Strausberg RL;Marie SK;Shinjo SM;Yan H;Riggins GJ;Bigner DD;Karchin R;Papadopoulos N;Parmigiani G;Vogelstein B;Velculescu VE;Kinzler KW
通讯作者：
Kinzler KW
影响因子：
14.9
作者：
Forbes SA;Bindal N;Bamford S;Cole C;Kok CY;Beare D;Jia M;Shepherd R;Leung K;Menzies A;Teague JW;Campbell PJ;Stratton MR;Futreal PA
通讯作者：
Futreal PA
影响因子：
3.2
作者：
Kovanich, Duangnapa;van der Heyden, Marcel A. G.;Scholten, Arjen
通讯作者：
Scholten, Arjen
影响因子：
64.8
作者：
LANDIS, CA;MASTERS, SB;VALLAR, L
通讯作者：
VALLAR, L