title: Genomic and proteomic characterization of ARID1A chromatin remodeller in ampullary tumors.
abstract: AT rich interactive domain 1A (ARID1A)is one of the most commonly mutated genes in a broad variety of tumors. The mechanisms that involveARID1Ain ampullary cancer progression remains elusive. Here, we evaluated the frequency ofARID1AandKRASmutations in ampullary adenomas and adenocarcinomas and in duodenal adenocarcinomas from two cohorts of patients from Singapore and Romania, correlated with clinical and pathological tumor features, and assessed the functional role ofARID1A. In the ampullary adenocarcinomas, the frequency ofKRASandARID1Amutations was 34.7% and 8.2% respectively, with a loss or reduction of ARID1A protein in 17.2% of the cases.ARID1Amutational status was significantly correlated with ARID1A protein expression level (P=0.023). There was a significant difference in frequency ofARID1Amutation between Romania and Singapore (2.7% versus 25%, P=0.04), suggestive of different etiologies. One somatic mutation was detected in the ampullary adenoma group.In vitrostudies indicated the tumor suppressive role ofARID1A. Our results warrant further investigation of this chromatin remodeller as a potential early biomarker of the disease, as well as identification of therapeutic targets inARID1Amutated ampullary cancers.
authors.affiliation: Laboratory of Cancer Epigenome, National Cancer Centre SingaporeSingapore; Centre of Digestive Diseases and Liver Transplantation, Fundeni Clinical InstituteBucharest, Romania.
authors.forename: Anca
authors.initials: A
authors.lastname: Nastase
authors.affiliation: Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital Singapore.
authors.forename: Jin Yao
authors.initials: JY
authors.lastname: Teo
authors.affiliation: Laboratory of Cancer Epigenome, National Cancer Centre Singapore Singapore.
authors.forename: Hong Lee
authors.initials: HL
authors.lastname: Heng
authors.affiliation: Laboratory of Cancer Epigenome, National Cancer Centre Singapore Singapore.
authors.forename: Cedric Chuan Young
authors.initials: CC
authors.lastname: Ng
authors.affiliation: Laboratory of Cancer Epigenome, National Cancer Centre Singapore Singapore.
authors.forename: Swe Swe
authors.initials: SS
authors.lastname: Myint
authors.affiliation: Laboratory of Cancer Epigenome, National Cancer Centre Singapore Singapore.
authors.forename: Vikneswari
authors.initials: V
authors.lastname: Rajasegaran
authors.affiliation: Laboratory of Cancer Epigenome, National Cancer Centre Singapore Singapore.
authors.forename: Jia Liang
authors.initials: JL
authors.lastname: Loh
authors.affiliation: Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital Singapore.
authors.forename: Ser Yee
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital Singapore.
authors.forename: London Lucien
authors.initials: LL
authors.lastname: Ooi
authors.affiliation: Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital Singapore.
authors.forename: Alexander Yaw Fui
authors.initials: AY
authors.lastname: Chung
authors.affiliation: Department of Surgical Oncology, National Cancer Centre Singapore Singapore.
authors.forename: Pierce Kah Hoe
authors.initials: PK
authors.lastname: Chow
authors.affiliation: Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital Singapore.
authors.forename: Peng Chung
authors.initials: PC
authors.lastname: Cheow
authors.affiliation: Department of Pathology, Singapore General Hospital Singapore, Singapore.
authors.forename: Wei Keat
authors.initials: WK
authors.lastname: Wan
authors.affiliation: Department of Pathology, Singapore General Hospital Singapore, Singapore.
authors.forename: Rafy
authors.initials: R
authors.lastname: Azhar
authors.affiliation: Department of Pathology, Singapore General Hospital Singapore, Singapore.
authors.forename: Avery
authors.initials: A
authors.lastname: Khoo
authors.affiliation: Department of Pathology, Singapore General Hospital Singapore, Singapore.
authors.forename: Sam Xin
authors.initials: SX
authors.lastname: Xiu
authors.affiliation: Department of Pathology, Singapore General Hospital Singapore, Singapore.
authors.forename: Syed Muhammad Fahmy
authors.initials: SM
authors.lastname: Alkaff
authors.affiliation: Program in Cancer and Stem Cell Biology, Duke-NUS Medical SchoolSingapore, Singapore; Centre for Computational Biology, Duke-NUS Medical SchoolSingapore, Singapore.
authors.forename: Ioana
authors.initials: I
authors.lastname: Cutcutache
authors.affiliation: Lymphoma Genomic Translational Research Laboratory, National Cancer Centre Singapore Singapore.
authors.forename: Jing Quan
authors.initials: JQ
authors.lastname: Lim
authors.affiliation: Lymphoma Genomic Translational Research Laboratory, National Cancer Centre Singapore Singapore.
authors.forename: Choon Kiat
authors.initials: CK
authors.lastname: Ong
authors.affiliation: Department of Pathology, Fundeni Clinical InstituteBucharest, Romania; Faculty of Medicine, Titu Maiorescu UniversityBucharest, Romania.
authors.forename: Vlad
authors.initials: V
authors.lastname: Herlea
authors.affiliation: Centre of Digestive Diseases and Liver Transplantation, Fundeni Clinical Institute Bucharest, Romania.
authors.forename: Simona
authors.initials: S
authors.lastname: Dima
authors.affiliation: Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School Boston, Massachusetts, USA.
authors.forename: Dan G
authors.initials: DG
authors.lastname: Duda
authors.affiliation: Laboratory of Cancer Epigenome, National Cancer Centre SingaporeSingapore; Program in Cancer and Stem Cell Biology, Duke-NUS Medical SchoolSingapore, Singapore; Cancer Science Institute of Singapore, National University of SingaporeSingapore, Singapore; Institute of Molecular and Cell Biology, ASTARSingapore, Singapore.
authors.forename: Bin Tean
authors.initials: BT
authors.lastname: Teh
authors.affiliation: Centre of Digestive Diseases and Liver Transplantation, Fundeni Clinical Institute Bucharest, Romania.
authors.forename: Irinel
authors.initials: I
authors.lastname: Popescu
authors.affiliation: Department of Pathology, Singapore General Hospital Singapore, Singapore.
authors.forename: Tony Kiat Hon
authors.initials: TK
authors.lastname: Lim
keywords: ARID1A; Ampullary cancer; KRAS; Sanger sequencing