Wang, Vivian W.

Personalized treatment of genetically stratified subgroups has the potential to improve outcomes in many malignant tumors. This study distills clinically meaningful prognostic/predictive genomic marker for cervical adenocarcinoma using signature genomic aberrations and single-point nonsynonymous mutation-specific droplet digital PCR (ddPCR). Mutations in PIK3CA E542K, E545K, or H1047R were detected in 41.7% of tumors. PIK3CA mutation detected in the patient’s circulating DNA collected before treatment or during follow-up was significantly associated with decreased progression-free survival or overall survival. PIK3CA mutation in the circulating DNA during follow-up after treatment predicted recurrence with 100% sensitivity and 64.29% specificity. It is the first indication of the predictive power of PIK3CA mutations in cervical adenocarcinoma. The work contributes to the development of liquid biopsies for follow up surveillance and a possibility of tailoring management of this particular women’s cancer.

Abstract Chromosome rearrangements that result in gene fusions have important roles in the initial steps of tumorigenesis especially in leukemias and lymphomas, but the biological and clinical impact of gene fusions in the common solid tumor has been less appreciated. We previously generated RNAseq data from 12 oropharyngeal tumors along with matched normal tissue from the same patients. We utilized and compared two bioinformatic pipelines, SnowShoes-FTD and FusionHunter to identify two novel fusion events involving of MGST3-ZMAT5 and MS4A7-DKFZp586P0123. These fusions were validated utilizing. Reverse transcriptase polymerase chain reaction (RT-PCR) and Sanger sequencing validated. In the first translocation the 5′ UTR of MGST3 was fused with exon 1 of ZMAT5, and in the second translocation the exon 2 of MS4A7 was fused with 3′ UTR of DKFZp586P0123. These precise fusions were not present in the matched normal tissue, however, they were only found in the single tumor in which they were identified. Given a growing and powerful set of high-throughput massively parallel sequencing technologies, the future for genome-wide analysis of chromosome rearrangement appears open in many directions. Ultimately, we hope that this integrative methodology will elucidate key aspects of tumor biology as well as generate novel targets for cancer diagnostics and therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3100. doi:1538-7445.AM2012-3100

Abstract MicroRNAs (miRNAs) play an important role in a variety of physiological processes as well as pathophysiological processes, including cancinogenesis. This study was to identify a distinct miRNA expression signature for cervical intraepithelial neoplasia (CIN) and to reveal individual miRNAs that may be involved in the development of cervical carcinoma. Expression profiling using quantitative real-time RT-PCR of 202 miRNAs was performed on micro-dissected high-grade CIN (CIN 2/3) tissues as compared to normal cervical epithelium. The expression of 12 miRNAs including miR-518a, miR-34b, miR-34c, miR-20b, miR-338, miR-9, miR-512-5p, miR-424, miR-345, miR-10a, miR-193b and miR-203 were significantly different between high-grade CIN and normal epithelium. This miRNA signature was further validated by an independent set of high-grade CIN tissue. The same characteristic signature can also be used to distinguish cervical squamous cell carcinoma (SCC) from normal controls. Target prediction analysis revealed that these dysregulated miRNAs control the apoptosis signaling pathway and cell cycle regulation. These findings contribute to understanding of the pathogenesis of cervical carcinoma at the molecular level. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5047. doi:1538-7445.AM2012-5047