Molecular Profiling Reveals Common and Specific Development Processes in Different Types of Gynecologic Cancers

Abstract

Background: Gynecologic cancers have become a major threat to women's health. The molecular biology of gynecologic cancers is not as well understood as that of breast cancer, and precision targeting is still new. Although viewed collectively as a group of cancers within the female reproductive system, they are more often studied separately. A comprehensive within-group comparison on molecular profiles is lacking.Methods: We conducted a whole-exome sequencing study of cervical/endometrial/ ovarian cancer samples from 209 Chinese patients. We combined our data with genomic and transcriptomic data from relevant TCGA cohorts to identify and verify common/ exclusive molecular changes in cervical/endometrial/ovarian cancer.Results: We identified shared molecular features including a COSMIC signature of deficient mismatch repair (dMMR), four recurrent copy-number variation (CNV) events, and extensive alterations in PI3K-Akt-mTOR signaling and cilium component genes; we also identified transcription factors and pathways that are exclusively altered in cervical/ endometrial/ovarian cancer. The functions of the commonly/exclusively altered genomic circuits suggest (1) a common reprogramming process during early tumor initiation, which involves PI3K activation, defects in mismatch repair and cilium organization, as well as disruption in interferon signaling and immune recognition; (2) a cell-type specific program at late-stage tumor development that eventually lead to tumor proliferation and migration. Conclusion:This study describes, from a molecular point of view, how similar and how different gynecologic cancers are, and it provides a hypothesis about the causes of the observed similarities and differences.

Precision medicine for cervical cancer

“…Whole-exome sequencing has identified frequent molecular alterations along the HER2/PIK3/ AKT/mTOR pathway [26,27]. Zammataro et al identified genomic alterations in the oncogene PIK3CA or the PIK3CA pathway, including derangements in HER2 expression, in 52% of cervical tumors, primarily consisting of missense mutations and amplifications.…”

Genomic Profiling of Chinese Cervical Cancer Patients Reveals Prevalence of DNA Damage Repair Gene Alterations and Related Hypoxia Feature

“…To our knowledge, there existed several studies describing genomic features of Chinese cervical cancer patients, namely, cervical cancer cases of Chinese Hong Kong women (14), endocervical adenocarcinoma cases (15), 32 cervical cancer cases (16), 32 advanced cervical cancer (17), and 74 cervical cancer cases (18) of Chinese mainland women. However, the latter two studies focused on the molecular profiles of integrated gynecologic cancers containing ovarian cancer, endometrial cancer, and cervical cancer.…”

Expression Profiles of Hypoxia-Related Genes of Cancers Originating from Anatomically Similar Locations Using TCGA Database Analysis

“…CESC and UCEC are representative gynecological cancers. Although these two cancer types have different clinical features, origins, and prognoses, studies have demonstrated that gynecologic cancers share abnormally expressed genes [14]. Two hub genes Two positive risk coefficient genes (ITGB1, LDHA) in the lung group were related to amino acid transport.…”