3q26 Amplifications in Cervical Squamous Carcinomas.

Curr Oncol

Algoma District Cancer Program, Sault Area Hospital, Sault Ste. Marie, ON P6B 0A8, Canada.

Published: July 2021

Background: Squamous carcinomas of the uterine cervix often carry mutations of the gene encoding for the catalytic sub-unit of kinase PI3K, . The locus of this gene at chromosome 3q26 and neighboring loci are also commonly amplified. The landscape of 3q26-amplified cases have not been previously characterized in detail in cervical cancer.

Methods: Published genomic data and associated clinical data from TCGA cervical cancer cohort were analyzed at cBioportal for amplifications in genes at 3q26. The clinical and molecular characteristics of the group of patients with 3q26 amplifications was compared with the group without 3q26 amplifications. Comparative prevalence of amplification and expression of genes at 3q26 in amplified squamous cervical cancer cases were surveyed as well as 3q26 amplifications in cervical cancer cell line databases.

Results: Amplification of 3q26 locus is a prevalent molecular lesion in cervical squamous cell carcinomas encountered in about 15% of cases in TCGA cohort of 247 patients. Cancer-related genes commonly amplified from 3q26 include , , ,  , , and TERC. Amplified cases do not completely overlap with mutant cases. Differences exist between 3q26-amplified and non-amplified carcinomas in the frequency of mutations and frequency of other amplifications. Most commonly over-expressed genes in 3q26 amplified cases include , , , and less commonly and .

Conclusion: The subset of squamous cervical carcinomas with 3q26 amplifications is not overlapping with cancers carrying mutations and contains, besides PIK3CA, other cancer-associated genes that are over-expressed at the mRNA level, including and . , a regulator of SCF ubiquitin ligase activity, may be a relevant pathogenic player given the importance of ubiquitination and the proteasome in the disease. These observations could form the basis for therapeutic exploitation in this subset of squamous cervical carcinomas.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395483PMC
http://dx.doi.org/10.3390/curroncol28040251DOI Listing

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