Genomic profiling of multifocal intrahepatic cholangiocarcinoma reveals intraindividual concordance of genetic alterations

Carcinogenesis. 2021 Apr 17;42(3):436-441. doi: 10.1093/carcin/bgaa124.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bile Duct Neoplasms / genetics*
  • Bile Duct Neoplasms / mortality
  • Bile Duct Neoplasms / pathology
  • Bile Duct Neoplasms / surgery
  • Bile Ducts, Intrahepatic / pathology
  • Bile Ducts, Intrahepatic / surgery
  • Biomarkers, Tumor / genetics*
  • Cholangiocarcinoma / genetics*
  • Cholangiocarcinoma / mortality
  • Cholangiocarcinoma / secondary
  • Cholangiocarcinoma / surgery
  • Clinical Decision-Making
  • Contraindications, Procedure
  • DNA Copy Number Variations
  • DNA Mutational Analysis
  • Diagnosis, Differential
  • Follow-Up Studies
  • Hepatectomy / adverse effects
  • High-Throughput Nucleotide Sequencing
  • Humans
  • INDEL Mutation
  • Liver / pathology
  • Liver / surgery
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / secondary
  • Liver Neoplasms / surgery
  • Lymph Node Excision / adverse effects
  • Lymph Nodes / pathology
  • Lymph Nodes / surgery
  • Lymphatic Metastasis / diagnosis
  • Lymphatic Metastasis / genetics*
  • Lymphatic Metastasis / pathology
  • Lymphatic Metastasis / therapy
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / prevention & control
  • Patient Selection
  • Point Mutation
  • Precision Medicine / methods
  • Progression-Free Survival

Substances

  • Biomarkers, Tumor