Abstract
It is well known that tumour initiation and progression are primarily an accumulation of genetic mutations. The mutation status of a tumour may predict prognosis and enable better selection of targeted therapies. In the current study, we analysed a total of 55 surgical tumours from stage IB-IIB cervical cancer (CC) patients who had undergone radical hysterectomy including pelvic lymphadenectomy, using a cancer panel covering 50 highly mutated tumorigenesis-related genes. In 35 patients (63.6%), a total 52 mutations were detected (58.3% in squamous cell carcinoma, 73.7% in adenocarcinoma), mostly in PIK3CA (34.5%) and KRAS and TP53 (9.1%). Being mutation-positive was significantly correlated with pelvic lymph node (PLN) metastasis (P = 0.035) and tended to have a worse overall survival (P = 0.076). In particular, in the patients with squamous cell carcinoma, there was a significant association between being mutation-positive and relapse-free survival (P = 0.041). The patients with PLN metastasis had a significantly worse overall survival than those without (P = 0.006). These results indicate that somatic mutation status is a predictive biomarker for PLN metastasis in early-stage CC, and is consequently related to poor prognosis. Therefore, comprehensive genetic mutations, rather than a single genetic mutation, should be examined widely in order to identify novel genetic indicators with clinical usefulness.
Highlights
It is well known that tumour initiation and progression are primarily an accumulation of genetic mutations
The 52 mutations were found in the following genes; PIK3CA (n = 19, 34.5% of the 55 tumours), KRAS and TP53 (n = 5 each, 9.1%), PTEN (n = 4, 7.3%), FBXW7 (n = 3, 5.5%), RB1 and GNAS (n = 2 each, 2.2%), as well as in AKT1, FGFR3, APC, ATM, CTCNB1, FGFR, ERBB4, KDR, KIT, NPM1, SMAD4 and STK11 (n = 1 each, 1.8%)
Our findings showed high rates of a potential oncogenic driver or drug targetable mutations in CC patients (Fig. 1)
Summary
It is well known that tumour initiation and progression are primarily an accumulation of genetic mutations. We analysed a total of 55 surgical tumours from stage IB-IIB cervical cancer (CC) patients who had undergone radical hysterectomy including pelvic lymphadenectomy, using a cancer panel covering 50 highly mutated tumorigenesis-related genes. The patients with PLN metastasis had a significantly worse overall survival than those without (P = 0.006) These results indicate that somatic mutation status is a predictive biomarker for PLN metastasis in early-stage CC, and is related to poor prognosis. For comprehensive elucidation of genetic alterations in cervical tumours, recurrent somatic mutations of MAPK1, HLA-B, EP300, FBXW7, NFE2L2, and ERBB2 in squamous cell carcinoma (SCC), as well as those of ELF3 and CBFB genes in adenocarcinoma (AC), have been identified using whole-exome sequencing analysis[12]. Study, we performed a systematic somatic mutation analysis in CC tumours using a cancer panel, and examined whether somatic mutations are associated with risk factors and prognosis in early-stage CC after RH
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
