The landscape of somatic mutations in Indonesian cervical cancer is predominated by the PI3K pathway

Abstract

Objective: To investigate the prevalence of somatic mutations in Indonesian cervical carcinoma patients in the context of histology and human papillomavirus (HPV) type.

Methods: In total 174 somatic hot-spot mutations in 13 genes were analyzed by mass spectrometry in 137 Indonesian cervical carcinomas.

Results: In 66/137 tumors (48%) 95 mutations were identified. PIK3CA was most frequently mutated (24%), followed by FBXW7 (7%), CTNNB1 (6%), and PTEN (6%). In squamous cell carcinomas more often multiple mutations per sample (p=0.040), and more PIK3CA (p=0.039) and CTNNB1 (p=0.038) mutations were detected compared to adenocarcinomas. PIK3CA mutations were associated with HPV 16 positivity, CDKN2A mutations with HPV 52 positivity, and, interestingly, PTEN mutations with HPV negativity. Balinese tumor samples more often carried multiple mutations (p=0.019), and more CTNNB1, CDKN2A, and NRAS mutations compared to Javanese tumor samples.

Conclusions: Potentially targetable somatic mutations occurred in 48% of Indonesian cervical carcinomas. The landscape of mutations is predominated by mutations concerning the PI3K pathway, and we prompt for more research on developing therapies targeting this pathway, explicitly for the more advanced stage cervical carcinoma patients.

Keywords: Cervical carcinoma; Indonesia; PIK3CA; cancer genomics; human papillomavirus; somatic mutation; targeting therapy.