IPMNs with co-occurring invasive cancers: neighbours but not always relatives.
IPMNs with co-occurring invasive cancers: neighbours but not always relatives.
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DOI：
10.1136/gutjnl-2017-315062
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发表时间：
2018-09
期刊：
影响因子：
24.5
通讯作者：
Wood, Laura D.
中科院分区：
文献类型：
--
作者：
Felsenstein, Matthaus;Noe, Michael;Masica, David L.;Hosoda, Waki;Chianchiano, Peter;Fischer, Catherine G.;Lionheart, Gemma;Brosens, Lodewijk A. A.;Pea, Antonio;Yu, Jun;Gemenetzis, Georgios;Groot, Vincent P.;Makary, Martin A.;He, Jin;Weiss, Matthew J.;Cameron, John L.;Wolfgang, Christopher L.;Hruban, Ralph H.;Roberts, Nicholas J.;Karchin, Rachel;Goggins, Michael G.;Wood, Laura D.
导管内乳头状粘液性肿瘤（IPMN）是可导致浸润性胰腺癌的前驱病变。虽然约8%的胰腺导管腺癌切除患者有一个共同发生的IPMN，这两个病变之间的确切的遗传关系还没有系统的研究。我们分析了一家医院10年来所有同时发生IPMN和浸润性胰腺癌的患者。对于每名患者，我们分别从癌、相邻IPMN和远端IPMN分离DNA，并对一组胰腺癌驱动基因进行靶向下一代测序。然后，我们使用鉴定的突变来推断IPMN和每个患者中共同发生的浸润性癌的相关性。我们分析了61例IPMN/导管腺癌患者以及13例IPMN/胶质癌患者和7例IPMN/壶腹区癌患者的共发IPMN和浸润性癌。在同时发生IPMN和导管腺癌的患者中，51%可能相关。令人惊讶的是，18%的共同发生的IPMN和导管腺癌可能是独立的，这表明癌来自一个独立的前体。相比之下，所有胶质癌都可能与其相关的IPMN有关。此外，这些分析表明，IPMN中存在显著的遗传异质性，即使是在充分表征的驱动基因方面。本研究表明，IPMN和导管腺癌可能独立并存的患病率高于以前的认识。这些发现对IPMN患者的分子危险分层具有重要意义。
Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions that can give rise to invasive pancreatic carcinoma. Although approximately 8% of patients with resected pancreatic ductal adenocarcinoma have a co-occurring IPMN, the precise genetic relationship between these two lesions has not been systematically investigated. We analysed all available patients with co-occurring IPMN and invasive intrapancreatic carcinoma over a 10-year period at a single institution. For each patient, we separately isolated DNA from the carcinoma, adjacent IPMN and distant IPMN and performed targeted next generation sequencing of a panel of pancreatic cancer driver genes. We then used the identified mutations to infer the relatedness of the IPMN and co-occurring invasive carcinoma in each patient. We analysed co-occurring IPMN and invasive carcinoma from 61 patients with IPMN/ductal adenocarcinoma as well as 13 patients with IPMN/colloid carcinoma and 7 patients with IPMN/carcinoma of the ampullary region. Of the patients with co-occurring IPMN and ductal adenocarcinoma, 51% were likely related. Surprisingly, 18% of co-occurring IPMN and ductal adenocarcinomas were likely independent, suggesting that the carcinoma arose from an independent precursor. By contrast, all colloid carcinomas were likely related to their associated IPMNs. In addition, these analyses showed striking genetic heterogeneity in IPMNs, even with respect to well-characterised driver genes. This study demonstrates a higher prevalence of likely independent co-occurring IPMN and ductal adenocarcinoma than previously appreciated. These findings have important implications for molecular risk stratification of patients with IPMN.
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影响因子：
64.8
作者：
Notta F;Chan-Seng-Yue M;Lemire M;Li Y;Wilson GW;Connor AA;Denroche RE;Liang SB;Brown AM;Kim JC;Wang T;Simpson JT;Beck T;Borgida A;Buchner N;Chadwick D;Hafezi-Bakhtiari S;Dick JE;Heisler L;Hollingsworth MA;Ibrahimov E;Jang GH;Johns J;Jorgensen LG;Law C;Ludkovski O;Lungu I;Ng K;Pasternack D;Petersen GM;Shlush LI;Timms L;Tsao MS;Wilson JM;Yung CK;Zogopoulos G;Bartlett JM;Alexandrov LB;Real FX;Cleary SP;Roehrl MH;McPherson JD;Stein LD;Hudson TJ;Campbell PJ;Gallinger S
通讯作者：
Gallinger S
影响因子：
7.3
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
通讯作者：
Scarpa, Aldo
DOI：
10.1158/1078-0432.ccr-14-2600
发表时间：
2015-04-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Dal Molin M;Zhang M;de Wilde RF;Ottenhof NA;Rezaee N;Wolfgang CL;Blackford A;Vogelstein B;Kinzler KW;Papadopoulos N;Hruban RH;Maitra A;Wood LD
通讯作者：
Wood LD
影响因子：
4.1
作者：
McCall, Chad M.;Mosier, Stacy;Eshleman, James R.
通讯作者：
Eshleman, James R.
影响因子：
3.8
作者：
Crippa, Stefano;Pergolini, Ilaria;Falconi, Massimo
通讯作者：
Falconi, Massimo