Molecular profiling of gynecologic cancers for treatment and management of disease - demonstrating clinical significance using the AMP/ASCO/CAP guidelines for interpretation and reporting of somatic variants

Cancer Genet. 2020 Apr:242:25-34. doi: 10.1016/j.cancergen.2019.11.008. Epub 2020 Jan 14.

Abstract

Molecular features of gynecologic cancers have been investigated in comprehensive studies, but correlation of these molecular signatures with clinical significance for precision medicine is yet to be established. Towards this end, we evaluated 95 gynecologic cancer cases submitted for testing using The JAX ActionSeq™ NGS panel. Molecular profiles were studied and compared to TCGA datasets to identify similarities and distinguishing features among subtypes. We identified 146 unique clinically significant variants (Tier I and II) across 45 of the 212 genes (21%), in 87% (83/95) of cases. TP53, PTEN, ARID1A, PIK3CA and ATM were the most commonly mutated genes; CCNE1 and ERBB2 amplifications were the most frequently detected copy-number alterations. PARP inhibitors were among the most commonly reported drug class with clinical trials, consistent with the frequency of DNA damage-response pathway mutations in our cohort. Overall, our study provides additional insight into the molecular profiles of gynecologic cancers, highlighting regulatory pathways involved, raising the potential implications for targeted therapeutic options currently available.

Keywords: Gynecological cancers; Molecular profiling; Next-generation sequencing.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • Cell Cycle / genetics
  • Cohort Studies
  • DNA Copy Number Variations
  • DNA Repair / genetics
  • DNA, Neoplasm / genetics
  • Datasets as Topic
  • Female
  • Gene Amplification
  • Gene Frequency
  • Genes, Neoplasm
  • Genital Neoplasms, Female / drug therapy
  • Genital Neoplasms, Female / genetics*
  • Genital Neoplasms, Female / pathology
  • Guideline Adherence
  • Humans
  • Middle Aged
  • Mutation*
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
  • Practice Guidelines as Topic*
  • Precision Medicine / methods
  • Retrospective Studies
  • Transcriptome*

Substances

  • Antineoplastic Agents
  • DNA, Neoplasm
  • Poly(ADP-ribose) Polymerase Inhibitors