Characterization of a new aggressive subtype of cervical cancer more common in minority populations using long-read whole genome sequencing

Authors

• S Tulsyan
• Y Xie
• I Rodriguez
• E Robinson
• E Gharzouzi
• R Orozco
• E Alvirez
• M Dean

Abstract

Our lab recently identified that YAP1 oncogene amplification is found to be associated with a 12 year earlier age-of-diagnosis, poorer survival and defies an aggressive subtype of cervical cancer. This subtype is more frequent in minority populations. The present study aims to characterize 24 YAP1 amplified cervical cancers from Guatemala and Venezuela via Oxford Nanopore technology (ONT) long-read sequencing. A total of 380 cervical cancer patients were assessed for YAP1 amplification using TaqMan assay. We found 45 samples to have YAP1 amplification. These 45 positive samples were subjected to whole genome barcode sequencing (coverage 5x) by ONT to visualize the YAP1 amplification status. 24 out of these 45 YAP1 amplified positive samples are being deep sequenced through library preparation via ONT-LSK114 chemistry. The frequency of somatic mutations in coding genes will be compared to 300 non-YAP1 amplified tumors from the same population characterized by whole exome sequencing. Presently, we have performed deep sequencing on 14 cervical tumors and 10 tumors reached sufficient coverage (25-30x) for further bioinformatic analysis. There is a higher frequency (8/10) of HPV integration in YAP1-amplified as compared to non-YAP1-amplified tumors. We found YAP1 amplifications include the BIRC2/3 genes and are caused by Breakage -Fusion- Bridge events. Therefore, YAP1-amplified subtype may contribute to health disparity and detailed characterization of this subtype may help to establish novel biomarkers for early cervical cancer screening and targeted therapy.

Scientific Focus Area: Genetics and Genomics

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