Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas

Yuchen Jiao; Timothy M. Pawlik; Robert A. Anders; Florin M. Selaru; Mirte M. Streppel; Donald J. Lucas; Noushin Niknafs; Violeta Beleva Guthrie; Anirban Maitra; Pedram Argani; G. Johan A. Offerhaus; Juan Carlos Roa; Lewis R. Roberts; Gregory J. Gores; Irinel Popescu; Sorin T. Alexandrescu; Simona Dima; Matteo Fassan; Michele Simbolo; Andrea Mafficini; Paola Capelli; Rita T. Lawlor; Andrea Ruzzenente; Alfredo Guglielmi; Giampaolo Tortora; Filippo De Braud; Aldo Scarpa; William Jarnagin; David Klimstra; Rachel Karchin; Victor E. Velculescu; Ralph H. Hruban; Bert Vogelstein; Kenneth W. Kinzler; Nickolas Papadopoulos; Laura D. Wood

doi:10.1038/ng.2813

Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas

Yuchen Jiao, Timothy M. Pawlik, Robert A. Anders, Florin M. Selaru, Mirte M. Streppel, Donald J. Lucas, Noushin Niknafs, Violeta Beleva Guthrie, Anirban Maitra, Pedram Argani, G. Johan A. Offerhaus, Juan Carlos Roa, Lewis R. Roberts, Gregory J. Gores, Irinel Popescu, Sorin T. Alexandrescu, Simona Dima, Matteo Fassan, Michele Simbolo, Andrea MafficiniPaola Capelli, Rita T. Lawlor, Andrea Ruzzenente, Alfredo Guglielmi, Giampaolo Tortora, Filippo De Braud, Aldo Scarpa, William Jarnagin, David Klimstra, Rachel Karchin, Victor E. Velculescu, Ralph H. Hruban, Bert Vogelstein, Kenneth W. Kinzler, Nickolas Papadopoulos, Laura D. Wood

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Abstract

Through exomic sequencing of 32 intrahepatic cholangiocarcinomas, we discovered frequent inactivating mutations in multiple chromatin-remodeling genes (including BAP1, ARID1A and PBRM1), and mutation in one of these genes occurred in almost half of the carcinomas sequenced. We also identified frequent mutations at previously reported hotspots in the IDH1 and IDH2 genes encoding metabolic enzymes in intrahepatic cholangiocarcinomas. In contrast, TP53 was the most frequently altered gene in a series of nine gallbladder carcinomas. These discoveries highlight the key role of dysregulated chromatin remodeling in intrahepatic cholangiocarcinomas.

Original language	English (US)
Pages (from-to)	1470-1473
Number of pages	4
Journal	Nature genetics
Volume	45
Issue number	12
DOIs	https://doi.org/10.1038/ng.2813
State	Published - Dec 2013

ASJC Scopus subject areas

Genetics

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Jiao, Y., Pawlik, T. M., Anders, R. A., Selaru, F. M., Streppel, M. M., Lucas, D. J., Niknafs, N., Guthrie, V. B., Maitra, A., Argani, P., Offerhaus, G. J. A., Roa, J. C., Roberts, L. R., Gores, G. J., Popescu, I., Alexandrescu, S. T., Dima, S., Fassan, M., Simbolo, M., ... Wood, L. D. (2013). Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas. Nature genetics, 45(12), 1470-1473. https://doi.org/10.1038/ng.2813

Jiao, Y, Pawlik, TM, Anders, RA , Selaru, FM, Streppel, MM, Lucas, DJ, Niknafs, N, Guthrie, VB, Maitra, A, Argani, P, Offerhaus, GJA, Roa, JC, Roberts, LR, Gores, GJ, Popescu, I, Alexandrescu, ST, Dima, S, Fassan, M, Simbolo, M, Mafficini, A, Capelli, P, Lawlor, RT, Ruzzenente, A, Guglielmi, A, Tortora, G, De Braud, F, Scarpa, A, Jarnagin, W, Klimstra, D, Karchin, R , Velculescu, VE , Hruban, RH , Vogelstein, B , Kinzler, KW , Papadopoulos, N & Wood, LD 2013, 'Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas', Nature genetics, vol. 45, no. 12, pp. 1470-1473. https://doi.org/10.1038/ng.2813

@article{43814f49330e4d9c88d05921957ea4c1,

title = "Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas",

abstract = "Through exomic sequencing of 32 intrahepatic cholangiocarcinomas, we discovered frequent inactivating mutations in multiple chromatin-remodeling genes (including BAP1, ARID1A and PBRM1), and mutation in one of these genes occurred in almost half of the carcinomas sequenced. We also identified frequent mutations at previously reported hotspots in the IDH1 and IDH2 genes encoding metabolic enzymes in intrahepatic cholangiocarcinomas. In contrast, TP53 was the most frequently altered gene in a series of nine gallbladder carcinomas. These discoveries highlight the key role of dysregulated chromatin remodeling in intrahepatic cholangiocarcinomas.",

author = "Yuchen Jiao and Pawlik, {Timothy M.} and Anders, {Robert A.} and Selaru, {Florin M.} and Streppel, {Mirte M.} and Lucas, {Donald J.} and Noushin Niknafs and Guthrie, {Violeta Beleva} and Anirban Maitra and Pedram Argani and Offerhaus, {G. Johan A.} and Roa, {Juan Carlos} and Roberts, {Lewis R.} and Gores, {Gregory J.} and Irinel Popescu and Alexandrescu, {Sorin T.} and Simona Dima and Matteo Fassan and Michele Simbolo and Andrea Mafficini and Paola Capelli and Lawlor, {Rita T.} and Andrea Ruzzenente and Alfredo Guglielmi and Giampaolo Tortora and {De Braud}, Filippo and Aldo Scarpa and William Jarnagin and David Klimstra and Rachel Karchin and Velculescu, {Victor E.} and Hruban, {Ralph H.} and Bert Vogelstein and Kinzler, {Kenneth W.} and Nickolas Papadopoulos and Wood, {Laura D.}",

note = "Funding Information: The authors wish to acknowledge the following funding sources: the Virginia and D.K. Ludwig Fund for Cancer Research; the Lustgarten Foundation for Pancreatic Cancer Research; US National Institutes of Health (NIH) grants P50 CA62924, K08DK090154 and EDRN U01CA086402; Associazione Italiana Ricerca Cancro (AIRC grants 12182, 11930, 6421 and IG 12214); and Italian Cancer Genome Project FIRB RBAP10AHJB.",

year = "2013",

month = dec,

doi = "10.1038/ng.2813",

language = "English (US)",

volume = "45",

pages = "1470--1473",

journal = "Nature genetics",

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T1 - Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas

AU - Jiao, Yuchen

AU - Pawlik, Timothy M.

AU - Anders, Robert A.

AU - Selaru, Florin M.

AU - Streppel, Mirte M.

AU - Lucas, Donald J.

AU - Niknafs, Noushin

AU - Guthrie, Violeta Beleva

AU - Maitra, Anirban

AU - Argani, Pedram

AU - Offerhaus, G. Johan A.

AU - Roa, Juan Carlos

AU - Roberts, Lewis R.

AU - Gores, Gregory J.

AU - Popescu, Irinel

AU - Alexandrescu, Sorin T.

AU - Dima, Simona

AU - Fassan, Matteo

AU - Simbolo, Michele

AU - Mafficini, Andrea

AU - Capelli, Paola

AU - Lawlor, Rita T.

AU - Ruzzenente, Andrea

AU - Guglielmi, Alfredo

AU - Tortora, Giampaolo

AU - De Braud, Filippo

AU - Scarpa, Aldo

AU - Jarnagin, William

AU - Klimstra, David

AU - Karchin, Rachel

AU - Velculescu, Victor E.

AU - Hruban, Ralph H.

AU - Vogelstein, Bert

AU - Kinzler, Kenneth W.

AU - Papadopoulos, Nickolas

AU - Wood, Laura D.

N1 - Funding Information: The authors wish to acknowledge the following funding sources: the Virginia and D.K. Ludwig Fund for Cancer Research; the Lustgarten Foundation for Pancreatic Cancer Research; US National Institutes of Health (NIH) grants P50 CA62924, K08DK090154 and EDRN U01CA086402; Associazione Italiana Ricerca Cancro (AIRC grants 12182, 11930, 6421 and IG 12214); and Italian Cancer Genome Project FIRB RBAP10AHJB.

PY - 2013/12

Y1 - 2013/12

N2 - Through exomic sequencing of 32 intrahepatic cholangiocarcinomas, we discovered frequent inactivating mutations in multiple chromatin-remodeling genes (including BAP1, ARID1A and PBRM1), and mutation in one of these genes occurred in almost half of the carcinomas sequenced. We also identified frequent mutations at previously reported hotspots in the IDH1 and IDH2 genes encoding metabolic enzymes in intrahepatic cholangiocarcinomas. In contrast, TP53 was the most frequently altered gene in a series of nine gallbladder carcinomas. These discoveries highlight the key role of dysregulated chromatin remodeling in intrahepatic cholangiocarcinomas.

AB - Through exomic sequencing of 32 intrahepatic cholangiocarcinomas, we discovered frequent inactivating mutations in multiple chromatin-remodeling genes (including BAP1, ARID1A and PBRM1), and mutation in one of these genes occurred in almost half of the carcinomas sequenced. We also identified frequent mutations at previously reported hotspots in the IDH1 and IDH2 genes encoding metabolic enzymes in intrahepatic cholangiocarcinomas. In contrast, TP53 was the most frequently altered gene in a series of nine gallbladder carcinomas. These discoveries highlight the key role of dysregulated chromatin remodeling in intrahepatic cholangiocarcinomas.

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JF - Nature genetics

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ER -

Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas

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