Next-Generation Sequencing in Gynaecological Tumours: The Prognostic and Predictive Value of the Most Common Mutations Found in Ovarian, Endometrial, and Cervical Tumours: Literature Review and the University Medical Centre Utrecht Next-Generation Sequencing Data

Abstract

Objective: To investigate whether next-generation sequencing (NGS) in ovarian and endometrial tumours can discover mutations with a relevant prognostic or predictive value. Methods: After a literature search, selected studies were critically appraised using the Quality in Prognostic Studies tool. Data on mutation incidence and correlations with prognostic and predictive items were extracted from relevant studies and compared to our own cohort consisting of 28 patients analysed using NGS. Results: Eight out of 739 articles were found eligible, including different tumour types. Prevalence of mutations in the KRAS gene ranged between 5.34 and 58.8% in ovarian cancer. Two studies showed a significant correlation between KRAS mutations and an improved disease free- and overall survival. Clinical data were available for 17 of our patients, mostly cases of endometrial carcinomas. KRAS, PIK3CA, CTNNB1, and TP53 were the most frequently mutated genes in endometrial carcinomas, and PTEN and CTNNB1 correlated with a higher FIGO stage. Conclusion: In the ovary KRAS mutation is associated with type I ovarian tumours (low-grade serous, mucinous, endometrioid, and clear-cell) and may seem to have a more favourable prognosis. The prognostic value of TP53 is still controversial. In endometrial tumours, PTEN shows a positive correlation with better prognosis. PIK3CA may have a correlation with poorer prognosis. CTNNB1 mutations in endometrial carcinomas could predict a worse prognosis.

The role of biomarkers in endometrial cancer and hyperplasia: a literature review

“…Mutations in CTNNB1 (Catenin Beta-1) are associated with higher FIGO stage and metastasis. TP53 mutations are common in type II cancers [22]. In other cancers, such as colorectal, MMR-deficient tumours have been shown to have higher response rates to anti-PD1 immunotherapy than MMR-proficient tumours [23], yet no significant results for this in endometrial cancer have been published to date.…”

Genomic determinants in advanced endometrial cancer patients with sustained response to hormonal therapy- case series and review of literature

“…NGS enables various applications including whole genome sequencing, whole exome sequencing, targeted resequencing, analysis of coding and non-coding RNA expression, alternative splicing and discovery of novel non-coding RNAs ( 11 ). Sequencing of mutations in diverse cancers shows the potential of discovering new diagnostic, prognostic, therapeutic, or predictive mutational statuses ( 16 ). There are few studies that explore the relationship between NGS molecular signatures and prognosis of EC.…”