Mutation profiling of uterine cervical cancer patients treated with definitive radiotherapy

Yuya Yoshimoto, Yasushi Sasaki, Kazutoshi Murata, Shin ei Noda, Yuhei Miyasaka, Junko Hamamoto, Mio Furuya, Junko Hirato, Yoshiyuki Suzuki, Tatsuya Ohno, Takashi Tokino, Takahiro Oike, Takashi Nakano

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Objective: To elucidate tumor mutation profiles associated with outcomes of uterine cervical cancer (UCC) patients treated with definitive radiotherapy. Methods: Ninety-eight patients with newly diagnosed and pathologically confirmed UCC (82 squamous cell carcinomas, 12 adenocarcinomas, and four adenosquamous carcinomas) who were treated with definitive radiotherapy were analyzed. DNA was extracted from pre-treatment tumor biopsy specimens. The exons of 409 cancer-related genes were sequenced using a next-generation sequencer. Genetic mutations were identified and analyzed for correlations with clinical outcome. Results: Recurrent mutations were observed in PIK3CA (35.7%), ARID1A (25.5%), NOTCH1 (19.4%), FGFR3 (16.3%), FBXW7 (19.4%), TP53 (13.3%), EP300 (12.2%), and FGFR4 (10.2%). The prevalence of mutations in FGFR family genes (i.e., FGFR1–4) was almost as high (24.5%) as that in PIK3CA and ARID1A, both of which are well-studied drivers of UCC. Fifty-five percent (21 of 38) of the identified FGFR mutations were located in the FGFR protein tyrosine kinase domain. Five-year progression-free survival (PFS) rates for FGFR mutation-positive patients (n = 24) were significantly worse than those for FGFR mutation-negative patients (n = 74) (43.9% vs. 68.5%, respectively; P = 0.010). Multivariate analysis identified FGFR mutations as significant predictors of worse 5 year PFS (P = 0.005), independent of clinicopathological variables. Conclusions: FGFR mutations are associated with worse PFS in UCC patients treated with definitive radiotherapy. These results warrant further validation in prospective studies.

Original languageEnglish
Pages (from-to)546-553
Number of pages8
JournalGynecologic Oncology
Volume159
Issue number2
DOIs
Publication statusPublished - 2020 Nov

Keywords

  • Cervical cancer
  • Definitive radiotherapy
  • Targeted therapy
  • Tumoral mutation profiles

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynaecology

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