Open AccessGenomic profiling of multifocal intrahepatic cholangiocarcinoma reveals intraindividual concordance of genetic alterations
Author(s) -
Sung Hwan Lee,
Ève Simoneau,
Tatiana V. Karpinets,
P. Andrew Futreal,
Jianjun Zhang,
Milind Javle,
Jianhua Zhang,
Jean Nicolas Vauthey,
Ju Seog Lee,
Jeannelyn S. Estrella,
Yun Shin Chun
Publication year - 2020
Publication title -
carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.688
H-Index - 204
eISSN - 1460-2180
pISSN - 0143-3334
DOI - 10.1093/carcin/bgaa124
Subject(s) - intrahepatic cholangiocarcinoma , concordance , stk11 , indel , msh2 , cdkn2a , exome , pathology , msh6 , exome sequencing , biology , medicine , cancer research , cancer , dna mismatch repair , gene , germline mutation , kras , genetics , mutation , dna repair , genotype , single nucleotide polymorphism
In multifocal intrahepatic cholangiocarcinoma (IHC), intrahepatic metastases (IM) represent a contraindication to surgical resection, whereas satellite nodules (SN) do not. However, no consensus criteria exist to distinguish IM from SN. The purpose of this study was to determine genetic alterations and clonal relationships in surgically resected multifocal IHC. Next-generation sequencing of 34 spatially separated IHC tumors was performed using a targeted panel of 201 cancer-associated genes. Proposed definitions in the literature were applied of SN located in the same liver segment and ≤2 cm from the primary tumor; and IM located in a different liver segment and/or >2 cm from the primary tumor. Somatic point mutations concordant across tumors from individual patients included BAP1, SMARCA4 and IDH1. Small insertions and deletions (indels) present at the same genome positions among all tumors from individuals included indels in DNA repair genes, CHEK1, ERCC5, ATR and MSH6. Copy number alterations were also similar between all tumors in each patient. In this cohort of multifocal IHC, genomic profiles were concordant across all tumors in each patient, suggesting a common progenitor cell origin, regardless of the location of tumors in the liver. The decision to perform surgery should not be based upon a perceived distinction between IM and SN.