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Genomic landscape of ERCC alterations in breast and gynecological cancers: implications for targeted therapy and VUS

Sezin Canbek1,2, Melisa Karaağaç3, Aleyna Ermiş3

  • 1Umraniye Research and Training Hospital, Medical Genetics Department, Istanbul, Turkey. sezin.canbek@ogr.iu.edu.tr.

Molecular Biology Reports
|August 21, 2026
PubMed
Abstract

Insights

Excision Repair Cross-Complementation (ERCC) gene mutations are found in 5.8% of solid tumors, particularly breast and gynecological cancers. Further research is needed to classify these ERCC alterations for personalized cancer therapy.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • The Excision Repair Cross-Complementation (ERCC) gene family is crucial for DNA repair via the Nucleotide Excision Repair (NER) pathway.
  • ERCC gene alterations contribute to cancer development and affect treatment responses.
  • The clinical significance of ERCC mutations in solid tumors is not well understood.

Purpose of the Study:

  • To investigate the clinical and genomic characteristics of ERCC gene mutations in cancer patients.
  • To identify ERCC mutations as potential predictive biomarkers for solid tumors.
  • To explore the therapeutic implications of ERCC alterations, especially in non-BRCA related cancers.

Main Methods:

  • Retrospective analysis of 550 cancer patients from 2017-2024 using a hereditary cancer Next-Generation Sequencing (NGS) panel.
  • Exclusion of dominant variants (e.g., BRCA1/2) to focus on ERCC mutations.
  • Analysis of tumor types, metastatic status, and receptor expression in patients with ERCC mutations.

Main Results:

  • ERCC mutations were detected in 5.8% of the cohort, predominantly in breast (40.7%), endometrial (22.2%), and ovarian cancers (7.4%).
  • ERCC2 (43.8%) and ERCC4 (25%) were the most frequently mutated genes, with missense variants being the most common type (68.8%).
  • A high proportion (87.5%) of identified ERCC alterations were classified as Variants of Uncertain Significance (VUS).

Conclusions:

  • ERCC alterations are significant in breast and gynecological cancers but are clinically underutilized.
  • The high VUS rate highlights the need for improved functional classification and database updates for ERCC mutations.
  • Profiling ERCC mutations can enhance personalized medicine, guiding the use of platinum-based therapies and PARP inhibitors in non-BRCA patients.
Keywords:
ERCC gene mutationsBreast cancerEndometrial cancerOvarian cancerPARP inhibitorsTargeted therapyVUS reclassification

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