BACKGROUND: BRCA-associated protein 1, an enzyme encoded by the BAP1 gene, is commonly mutated in uveal melanoma, mesothelioma, and renal cancers. Tumors with BAP1 mutation follow an aggressive course. BAP1 mutations have also been observed in cholangiocarcinoma (CCA). The clinical phenotype of BAP1 mutant CCA may yield useful prognostic and therapeutic information but has not been defined. METHODS: The records of CCA patients who underwent next-generation sequencing (NGS) were reviewed, and data on clinical, histopathological, genetic, and radiological features; response to therapy; time to progression; and survival were analyzed. RESULTS: Twenty-two cases of BAP1-mutation associated CCA were diagnosed from January 1, 2009, to February 1, 2015, at our center. Twenty patients had intrahepatic CCA and two had extrahepatic CCA. Tumor sizes (largest dimension) ranged from 2 to 16 cm (mean, 8.5 cm). Twelve patients had tumors that were poorly differentiated. Majority of the patients had advanced disease at presentation and 13 had bone metastases. Thirteen patients (59%) experienced rapidly progressive disease following primary therapy (chemotherapy or surgical resection). The mean time to tumor progression was 3.8 months after the first line chemotherapy. CONCLUSIONS: BAP1 mutation in CCA may be associated with aggressive disease and poor response to standard therapies. Therefore, BAP1-targeted therapies need to be investigated.
BACKGROUND: BRCA-associated protein 1, an enzyme encoded by the BAP1 gene, is commonly mutated in uveal melanoma, mesothelioma, and renal cancers. Tumors with BAP1 mutation follow an aggressive course. BAP1 mutations have also been observed in cholangiocarcinoma (CCA). The clinical phenotype of BAP1 mutant CCA may yield useful prognostic and therapeutic information but has not been defined. METHODS: The records of CCA patients who underwent next-generation sequencing (NGS) were reviewed, and data on clinical, histopathological, genetic, and radiological features; response to therapy; time to progression; and survival were analyzed. RESULTS: Twenty-two cases of BAP1-mutation associated CCA were diagnosed from January 1, 2009, to February 1, 2015, at our center. Twenty patients had intrahepatic CCA and two had extrahepatic CCA. Tumor sizes (largest dimension) ranged from 2 to 16 cm (mean, 8.5 cm). Twelve patients had tumors that were poorly differentiated. Majority of the patients had advanced disease at presentation and 13 had bone metastases. Thirteen patients (59%) experienced rapidly progressive disease following primary therapy (chemotherapy or surgical resection). The mean time to tumor progression was 3.8 months after the first line chemotherapy. CONCLUSIONS:BAP1 mutation in CCA may be associated with aggressive disease and poor response to standard therapies. Therefore, BAP1-targeted therapies need to be investigated.
Entities:
Keywords:
BAP1-mutant cholangiocarcinoma; Foundation Medicine; cisplatin; gemcitabine; next-generation sequencing (NGS)
Authors: Aaron McKenna; Matthew Hanna; Eric Banks; Andrey Sivachenko; Kristian Cibulskis; Andrew Kernytsky; Kiran Garimella; David Altshuler; Stacey Gabriel; Mark Daly; Mark A DePristo Journal: Genome Res Date: 2010-07-19 Impact factor: 9.043
Authors: J William Harbour; Michael D Onken; Elisha D O Roberson; Shenghui Duan; Li Cao; Lori A Worley; M Laurin Council; Katie A Matatall; Cynthia Helms; Anne M Bowcock Journal: Science Date: 2010-11-04 Impact factor: 47.728
Authors: Juan Valle; Harpreet Wasan; Daniel H Palmer; David Cunningham; Alan Anthoney; Anthony Maraveyas; Srinivasan Madhusudan; Tim Iveson; Sharon Hughes; Stephen P Pereira; Michael Roughton; John Bridgewater Journal: N Engl J Med Date: 2010-04-08 Impact factor: 91.245
Authors: Eric Tran; Simon Turcotte; Alena Gros; Paul F Robbins; Yong-Chen Lu; Mark E Dudley; John R Wunderlich; Robert P Somerville; Katherine Hogan; Christian S Hinrichs; Maria R Parkhurst; James C Yang; Steven A Rosenberg Journal: Science Date: 2014-05-09 Impact factor: 47.728
Authors: 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 Journal: Nat Genet Date: 2013-11-03 Impact factor: 38.330
Authors: Thomas Wiesner; Anna C Obenauf; Rajmohan Murali; Isabella Fried; Klaus G Griewank; Peter Ulz; Christian Windpassinger; Werner Wackernagel; Shea Loy; Ingrid Wolf; Agnes Viale; Alex E Lash; Mono Pirun; Nicholas D Socci; Arno Rütten; Gabriele Palmedo; David Abramson; Kenneth Offit; Arthur Ott; Jürgen C Becker; Lorenzo Cerroni; Heinz Kutzner; Boris C Bastian; Michael R Speicher Journal: Nat Genet Date: 2011-08-28 Impact factor: 38.330
Authors: Chaitanya R Churi; Rachna Shroff; Ying Wang; Asif Rashid; HyunSeon C Kang; Jacqueline Weatherly; Mingxin Zuo; Ralph Zinner; David Hong; Funda Meric-Bernstam; Filip Janku; Christopher H Crane; Lopa Mishra; Jean-Nicholas Vauthey; Robert A Wolff; Gordon Mills; Milind Javle Journal: PLoS One Date: 2014-12-23 Impact factor: 3.240
Authors: Andreas Gnirke; Alexandre Melnikov; Jared Maguire; Peter Rogov; Emily M LeProust; William Brockman; Timothy Fennell; Georgia Giannoukos; Sheila Fisher; Carsten Russ; Stacey Gabriel; David B Jaffe; Eric S Lander; Chad Nusbaum Journal: Nat Biotechnol Date: 2009-02-01 Impact factor: 54.908
Authors: Sebastian Walpole; Antonia L Pritchard; Colleen M Cebulla; Robert Pilarski; Meredith Stautberg; Frederick H Davidorf; Arnaud de la Fouchardière; Odile Cabaret; Lisa Golmard; Dominique Stoppa-Lyonnet; Erin Garfield; Ching-Ni Njauw; Mitchell Cheung; Joni A Turunen; Pauliina Repo; Reetta-Stiina Järvinen; Remco van Doorn; Martine J Jager; Gregorius P M Luyten; Marina Marinkovic; Cindy Chau; Miriam Potrony; Veronica Höiom; Hildur Helgadottir; Lorenza Pastorino; William Bruno; Virginia Andreotti; Bruna Dalmasso; Giulia Ciccarese; Paola Queirolo; Luca Mastracci; Karin Wadt; Jens Folke Kiilgaard; Michael R Speicher; Natasha van Poppelen; Emine Kilic; Rana'a T Al-Jamal; Irma Dianzani; Marta Betti; Carsten Bergmann; Sandro Santagata; Sonika Dahiya; Saleem Taibjee; Jo Burke; Nicola Poplawski; Sally J O'Shea; Julia Newton-Bishop; Julian Adlard; David J Adams; Anne-Marie Lane; Ivana Kim; Sonja Klebe; Hilary Racher; J William Harbour; Michael L Nickerson; Rajmohan Murali; Jane M Palmer; Madeleine Howlie; Judith Symmons; Hayley Hamilton; Sunil Warrier; William Glasson; Peter Johansson; Carla Daniela Robles-Espinoza; Raul Ossio; Annelies de Klein; Susana Puig; Paola Ghiorzo; Maartje Nielsen; Tero T Kivelä; Hensin Tsao; Joseph R Testa; Pedram Gerami; Marc-Henri Stern; Brigitte Bressac-de Paillerets; Mohamed H Abdel-Rahman; Nicholas K Hayward Journal: J Natl Cancer Inst Date: 2018-12-01 Impact factor: 13.506
Authors: T J Ettrich; D Schwerdel; A Dolnik; F Beuter; T J Blätte; S A Schmidt; N Stanescu-Siegmund; J Steinacker; R Marienfeld; A Kleger; L Bullinger; T Seufferlein; A W Berger Journal: Sci Rep Date: 2019-09-13 Impact factor: 4.379
Authors: Neil Farquhar; Sophie Thornton; Sarah E Coupland; Judy M Coulson; Joseph J Sacco; Yamini Krishna; Heinrich Heimann; Azzam Taktak; Colleen M Cebulla; Mohamed H Abdel-Rahman; Helen Kalirai Journal: J Pathol Clin Res Date: 2017-11-13