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 paraffinembedded (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.

Genomic analysis of pancreatic juice DNA assesses malignant risk of intraductal papillary mucinous neoplasm of pancreas

“…With this method, we not only detected critical mutations such as KRAS and GNAS, known markers in IPMN that prove to a certain extent the reliability of this sample source, but also found out that the mutation burden is significantly correlated with IPMN histologic grade which has been also previously reported in late stages of gynecologic cancers. [46][47][48] This correlation of mutation burden with histologic grade can be associated not only with the development of malignancy in IPMN, but also with the genomic heterogeneity inherent to advanced tumor samples and our distinct sampling method; different cell populations might possess singular mutations that could go undetected by traditional sampling, but they may be able to be observed on its entirety by the use of liquid biopsies, which have the potential to gather information from all the cell populations.…”

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

“…All patients had undergone adjuvant chemotherapy with capecitabine plus oxaliplatin (XELOX). The median number of chemotherapy cycles was 6 (range, [3][4][5][6][7][8][9][10][11][12]. Overall survival (OS) was defined as the time from surgery to death or the last follow-up.…”

Impact of Age on Tumor Mutation Burden in Gastric patients:a secondary analysis based on a cross-sectional study

“…As far as we know, there were limited studies about the impact of age on TMB. Similarly, Wang et al r eported that younger gynecologic cancer patients (age <40 years) had a significantly lower TMB than older patients (age ≥40 years) [25]. In an initial clinical cohort of 102,292 samples for 167 distinct can cer types, a significant increase in TMB associated with increased age was documented [26].This phen omenon could be explained by age-related somatic mutations in cancer genome.…”