medwireNews: A comprehensive genomic and molecular analysis of cervical cancers provides insight into potential therapeutic targets and identifies distinct molecular subtypes of the disease.
Using whole-exome sequencing, the researchers analyzed 192 samples from women with cervical cancer naïve to radiotherapy or chemotherapy, and identified 14 significantly mutated genes, of which SHKBP1, ERBB3, CASP8, HLA-A, and TGFBR2 had not been previously associated with cervical cancer.
They also detected amplifications involving the CD274 and PDCD1LG2 genes, which code for the immune checkpoint proteins PD-L1 and PD-L2, respectively, and BCAR4, a long noncoding RNA that promotes metastasis in breast cancer via the HER2/3 pathway and can be targeted indirectly by lapatinib.
These findings provide “rationales for developing clinical trials to treat populations of cervical cancer patients with distinct therapies,” say Akinyemi Ojesina (University of Alabama at Birmingham, USA) and fellow members of The Cancer Genome Atlas (TCGA) Research Network.
Integrated analyses of a subset of 178 specimens showed that cervical carcinoma could be classified into three subtypes, namely, squamous with high expression of keratin gene family members, squamous with low expression of these genes, or adenocarcinoma-rich. As reported in Nature, these subgroups have distinct patterns of somatic alterations, and are associated with different human papillomavirus features.
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