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KRAS Mutation in Rare Tumors: A Landscape Analysis of 3453 Chinese Patients

Shuhang Wang1, Qin Li2, Peiwen Ma1

  • 1Clinical Cancer Centre, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Frontiers in Molecular Biosciences
|April 1, 2022
PubMed

Insights

KRAS mutations occur in 8.7% of rare tumors, with varied subtypes. This landscape analysis suggests targeted and immunotherapy are feasible for these patients, impacting future clinical trials.

Area of Science:

  • Oncology
  • Genomics
  • Cancer Research

Background:

  • KRAS is a frequently mutated oncogene in human cancers, with recent advances in targeted and immunotherapy.
  • A comprehensive understanding of the KRAS molecular landscape in rare tumors is currently lacking.
  • KRAS mutations play a critical role in cancer development and progression.

Purpose of the Study:

  • To investigate the molecular landscape of KRAS mutations in a large cohort of rare tumors.
  • To identify the frequency, subtypes, and co-occurring alterations of KRAS mutations in rare tumor systems.
  • To explore the potential implications for targeted therapy and immunotherapy in KRAS-mutated rare tumors.

Main Methods:

  • Retrospective analysis of clinical samples from 3,453 patients with rare tumors (September 2015 - September 2021).
  • Hybrid-capture-based next-generation sequencing for genomic profiling.
  • Immunohistochemistry assay for PD-L1 expression analysis.

Main Results:

  • KRAS mutations were identified in 8.7% of patients, with significant variation across tumor types.
  • G12D (29.2%), G12V (24.6%), and G13D (10.8%) were the most common KRAS mutations.
  • KRAS G12C mutations were found in specific rare tumors like lung sarcomatoid carcinoma (5.7%) and ovarian clear cell carcinoma (5.4%).
  • 31.8% of KRAS mutations and 36.4% of KRAS G12C mutations co-occurred with other targetable alterations.
  • No significant correlation was observed between KRAS mutation status and TMB-H, MSI-H, or PD-L1 status.

Conclusions:

  • This study provides the first large-scale KRAS mutation landscape analysis in rare tumors globally and in China.
  • The findings suggest that both targeted therapy and immunotherapy are potentially viable treatment options for patients with KRAS-mutated rare tumors.
  • Understanding the KRAS mutation landscape is crucial for guiding clinical trial design and treatment strategies for rare tumors in China.
Keywords:
G12CKRASimmunotherapyrare tumorstargeted therapy

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