Targeted next-generation sequencing of cancer genes dissects the molecular profiles of intraductal papillary neoplasms of the pancreas.
Targeted next-generation sequencing of cancer genes dissects the molecular profiles of intraductal papillary neoplasms of the pancreas.
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DOI：
10.1002/path.4344
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发表时间：
2014-07
影响因子：
7.3
通讯作者：
Scarpa, Aldo
中科院分区：
文献类型：
--
作者：
Amato, Eliana;dal Molin, Marco;Mafficini, Andrea;Yu, Jun;Malleo, Giuseppe;Rusev, Borislav;Fassan, Matteo;Antonello, Davide;Sadakari, Yoshihiko;Castelli, Paola;Zamboni, Giuseppe;Maitra, Anirban;Salvia, Roberto;Hruban, Ralph H.;Bassi, Claudio;Capelli, Paola;Lawlor, Rita T.;Goggins, Michael;Scarpa, Aldo
导管内肿瘤是侵袭性胰腺癌的重要先兆，为在侵袭性癌发生之前发现和治疗胰腺肿瘤提供了机会。对这些病变的诊断评估具有挑战性，因为诊断成像和细胞学采样不能提供关于病变分类、不典型增生级别或是否存在侵袭的准确信息。此外，这些前驱病变的分子驱动基因突变还没有完全确定。对52例导管内乳头状肿瘤，包括48例导管内乳头状粘液性肿瘤(IPMN)和4例导管内乳头状瘤(ITPN)进行了51个癌相关基因的突变检测，采用基于离子流半导体的下一代测序技术。对34例IPMN和17例IPMN相关癌进行P16和Smad4免疫组织化学染色。在46/48(96%)的IPMN中观察到至少一个体细胞突变，29(60%)有多个基因改变。44/48(92%)的IPMN存在GNAS和/或KRAS突变。48例IPMN中有38例(79%)发生GNAS突变，24例(50%)发生KRAS突变，18例(37.5%)同时存在这两种突变。RNF43是第三个最常见的突变基因，总是与GNAS和/或KRAS突变有关，几乎所有在其他基因中发现的低频突变都是如此。TP53和BRAF基因突变(10%和6%)仅见于高级别IPMN。P16在7/34例IPMN和9/17例IPMN相关癌中缺失，1/34例IPMN和5/17例IPMN相关癌中Smad4缺失。与IPMN相比，四个ITPNS中只有一个有可检测到的驱动基因(GNAS和NRAS)突变。来自7个囊液抽吸物的DNA深度测序确定了在其相关的IPMN中检测到的13个突变中的10个。使用下一代测序来检测囊液突变有可能改善胰腺囊性肿瘤的诊断和预后分层。
Intraductal neoplasms are important precursors to invasive pancreatic cancer and provide an opportunity to detect and treat pancreatic neoplasia before an invasive carcinoma develops. The diagnostic evaluation of these lesions is challenging, as diagnostic imaging and cytological sampling do not provide accurate information on lesion classification, the grade of dysplasia or the presence of invasion. Moreover, the molecular driver gene mutations of these precursor lesions have yet to be fully characterized. Fifty-two intraductal papillary neoplasms, including 48 intraductal papillary mucinous neoplasms (IPMNs) and four intraductal tubulopapillary neoplasms (ITPNs), were subjected to the mutation assessment in 51 cancer-associated genes, using ion torrent semiconductor-based next-generation sequencing. P16 and Smad4 immunohistochemistry was performed on 34 IPMNs and 17 IPMN-associated carcinomas. At least one somatic mutation was observed in 46/48 (96%) IPMNs; 29 (60%) had multiple gene alterations. GNAS and/or KRAS mutations were found in 44/48 (92%) of IPMNs. GNAS was mutated in 38/48 (79%) IPMNs, KRAS in 24/48 (50%) and these mutations coexisted in 18/48 (37.5%) of IPMNs. RNF43 was the third most commonly mutated gene and was always associated with GNAS and/or KRAS mutations, as were virtually all the low-frequency mutations found in other genes. Mutations in TP53 and BRAF genes (10% and 6%) were only observed in high-grade IPMNs. P16 was lost in 7/34 IPMNs and 9/17 IPMN-associated carcinomas; Smad4 was lost in 1/34 IPMNs and 5/17 IPMN-associated carcinomas. In contrast to IPMNs, only one of four ITPNs had detectable driver gene (GNAS and NRAS) mutations. Deep sequencing DNA from seven cyst fluid aspirates identified 10 of the 13 mutations detected in their associated IPMN. Using next-generation sequencing to detect cyst fluid mutations has the potential to improve the diagnostic and prognostic stratification of pancreatic cystic neoplasms.
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影响因子：
4.1
作者：
Beadling, Carol;Neff, Tanaya L.;Corless, Christopher L.
通讯作者：
Corless, Christopher L.
影响因子：
6
作者：
Sato, N;Rosty, C;Goggins, M
通讯作者：
Goggins, M
影响因子：
11.5
作者：
Schoenleben, Frank;Qiu, Wanglong;Su, Gloria H.
通讯作者：
Su, Gloria H.
影响因子：
64.8
作者：
Biankin, Andrew V.;Waddell, Nicola;Kassahn, Karin S.;Gingras, Marie-Claude;Muthuswamy, Lakshmi B.;Johns, Amber L.;Miller, David K.;Wilson, Peter J.;Patch, Ann-Marie;Wu, Jianmin;Chang, David K.;Cowley, Mark J.;Gardiner, Brooke B.;Song, Sarah;Harliwong, Ivon;Idrisoglu, Senel;Nourse, Craig;Nourbakhsh, Ehsan;Manning, Suzanne;Wani, Shivangi;Gongora, Milena;Pajic, Marina;Scarlett, Christopher J.;Gill, Anthony J.;Pinho, Andreia V.;Rooman, Ilse;Anderson, Matthew;Holmes, Oliver;Leonard, Conrad;Taylor, Darrin;Wood, Scott;Xu, Qinying;Nones, Katia;Fink, J. Lynn;Christ, Angelika;Bruxner, Tim;Cloonan, Nicole;Kolle, Gabriel;Newell, Felicity;Pinese, Mark;Mead, R. Scott;Humphris, Jeremy L.;Kaplan, Warren;Jones, Marc D.;Colvin, Emily K.;Nagrial, Adnan M.;Humphrey, Emily S.;Chou, Angela;Chin, Venessa T.;Chantrill, Lorraine A.;Mawson, Amanda;Samra, Jaswinder S.;Kench, James G.;Lovell, Jessica A.;Daly, Roger J.;Merrett, Neil D.;Toon, Christopher;Epari, Krishna;Nguyen, Nam Q.;Barbour, Andrew;Zeps, Nikolajs;Kakkar, Nipun;Zhao, Fengmei;Wu, Yuan Qing;Wang, Min;Muzny, Donna M.;Fisher, William E.;Brunicardi, F. Charles;Hodges, Sally E.;Reid, Jeffrey G.;Drummond, Jennifer;Chang, Kyle;Han, Yi;Lewis, Lora R.;Dinh, Huyen;Buhay, Christian J.;Beck, Timothy;Timms, Lee;Sam, Michelle;Begley, Kimberly;Brown, Andrew;Pai, Deepa;Panchal, Ami;Buchner, Nicholas;De Borja, Richard;Denroche, Robert E.;Yung, Christina K.;Serra, Stefano;Onetto, Nicole;Mukhopadhyay, Debabrata;Tsao, Ming-Sound;Shaw, Patricia A.;Petersen, Gloria M.;Gallinger, Steven;Hruban, Ralph H.;Maitra, Anirban;Iacobuzio-Donahue, Christine A.;Schulick, Richard D.;Wolfgang, Christopher L.;Morgan, Richard A.;Lawlor, Rita T.;Capelli, Paola;Corbo, Vincenzo;Scardoni, Maria;Tortora, Giampaolo;Tempero, Margaret A.;Mann, Karen M.;Jenkins, Nancy A.;Perez-Mancera, Pedro A.;Adams, David J.;Largaespada, David A.;Wessels, Lodewyk F. A.;Rust, Alistair G.;Stein, Lincoln D.;Tuveson, David A.;Copeland, Neal G.;Musgrove, Elizabeth A.;Scarpa, Aldo;Eshleman, James R.;Hudson, Thomas J.;Sutherland, Robert L.;Wheeler, David A.;Pearson, John V.;McPherson, John D.;Gibbs, Richard A.;Grimmond, Sean M.
通讯作者：
Grimmond, Sean M.
影响因子：
4.6
作者：
Furukawa, Toru;Kuboki, Yuko;Tanji, Etsuko;Yoshida, Shoko;Hatori, Takashi;Yamamoto, Masakazu;Shibata, Noriyuki;Shimizu, Kyoko;Kamatani, Naoyuki;Shiratori, Keiko
通讯作者：
Shiratori, Keiko