Molecular profiles and tumor mutational burden analysis in Chinese patients with gynecologic cancers

Abstract

The goal of this work was to investigate the tumor mutational burden (TMB) in Chinese patients with gynecologic cancer. In total, 117 patients with gynecologic cancers were included in this study. Both tumor DNA and paired blood cell genomic DNA were isolated from formalin-fixed paraffin-embedded (FFPE) specimens and blood samples, and next-generation sequencing was performed to identify somatic mutations. TP53, PTEN, ARID1A, and PIK3CA alterations were significantly different in various types of gynecologic cancers (p = 0.001, 1.15E-07, 0.004, and 0.009, respectively). The median TMB of all 117 gynecologic tumor specimens was 0.37 mutations/Mb, with a range of 0–41.45 mutations/Mb. Despite the lack of significant difference, endometrial cancer cases had a higher median TMB than cervical and ovarian cancer cases. Younger gynecologic cancer patients (age <40 years) had a significantly lower TMB than older patients (age ≥40 years) (p = 0.04). In addition, TMB was significantly increased with increasing clinical stage of disease (p = 0.001). PTEN alterations were commonly observed in patients with a moderate to high TMB (n = 8, 38.10%, p = 9.95E-04). Although limited by sample size, all of the patients with TSC2 (n = 3, p = 3.83E-11) or POLE (n = 2, p = 0.005) mutations had a moderate to high TMB. Further large-scale, prospective studies are needed to validate our findings.

Clinical relevance of oncogenic driver mutations identified in endometrial carcinoma

“…Our findings showed a very high rate (91%) of a potential oncogenic driver or drug targetable mutations in EC patients. Validated mutations have been also reported in 78–94% of EC patients using a cancer panel [ 14 , 15 ], and EC is known as a tumor with a high frequency of mutated genes [16] . A comprehensive genomic analysis by The Cancer Genome Atlas (TCGA) resulted in the molecular classification of EC into four distinct subgroups [6] : the DNA polymerase epsilon (POLE) group, which has an exceedingly high mutation rate in conjunction with somatic mutations in the exonuclease domain of POLE ; the microsatellite instability (MSI) group, which has a high mutation rate and is a hallmark of a defective mismatch repair system because of hypermethylation of the MLH1 promoter or a germline mutation in one of the mismatch repair genes; the copy number (CN)-low group, which has a low mutation rate and most of the microsatellite stable EEC; and the CN-high group, which has a low mutation rate and consists serous carcinoma with extensive high-level CN alterations and frequent somatic mutations in TP53 .…”

A comprehensive analysis of somatic alterations in Chinese ovarian cancer patients

“…Wang et al . investigated the molecular profiles and analyzed TMB in Chinese patients with gynecological cancers, including ovarian, cervical, and endometrial cancers, and found that the mutation of BRCA1 was associated with higher TMB in ovarian cancer patients 52 . Birkbak et al .…”

Prognostic impact of gene copy number instability and tumor mutation burden in patients with resectable gastric cancer

“…Small panels based on next‐generation sequencing, such as FoundationOne CDx and MSK‐IMPACT, are widely used for selecting appropriate treatment approaches (such as targeted therapies, immunotherapies, and chemotherapies) with the advantages of a higher sequencing depth and more cost‐effectiveness than whole‐exome sequencing (WES). Previous studies have demonstrated that molecular characteristics based on the designed cancer‐related gene panel were consistent with those determined by WES and could be prognostic markers for various cancer types [6‐8]. As such, we analyzed the molecular features with the designed panel to investigate probable prognostic biomarkers for Chinese patients with GC.…”