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Journal of Gastrointestinal & Digestive System | ISSN: 2161-069X | Volume: 8
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October 29-30, 2018 | San Francisco, USA
International Conference on
Gastrointestinal Cancer and Therapeutics
4th World Congress on
Digestive & Metabolic Diseases
26th Annual Congress on
Cancer Science and Targeted Therapies
Large chromosomal rearrangements yield biomarkers to distinguish low-risk from intermediate and
high-risk prostate cancer
Farhad Kosari
Mayo Clinic, USA
Background: We tested the hypothesis that chromosomal rearrangements (CRs) could separate low-risk of progression (LRP)
from an intermediate and high risk of progression (IHRP) prostate cancer (PCa), and if these CRs have the potential to identify
men with LRP on needle biopsy that harbor IHRP PCa in the prostate gland.
Methods: Mate Pair sequencing of amplified DNA from pure populations of Gleason patterns (GPs) in 154 frozen specimens
from 126 patients was used to detect CRs. A custom bioinformatics pipeline identified abnormal junctions and copy number
variations (CNVs). Chromosomal instability was approximated by the number of abnormal junctions. Potential CR biomarkers
with the higher incidence of IHRP than in LRP and having significance in PCa biology were identified. Independent marker
validation was performed by FISH in a set of 152 archived specimens from 124 patients.
Results: The number of abnormal junctions did not distinguish LRP from IHRP. Loci corresponding to genes implicated in
PCa were more frequently altered in IHRP. Integrated analysis of CNVs and microarray data yielded six potential markers that
were more frequently detected in the GP3 of a Gleason score of 7 (GS7) PCa compared to GP3 in a GS6 PCa. Five of those
were cross-validated in an independent sample-set with statistically significant AUCs. Probes detecting deletions in PTEN and
CHD1 had AUCs of 0.87 and 0.73, respectively, and probes detecting gains in ASAP1, MYC, and HDAC9 had AUCs of 0.71,
0.82, and 0.77, respectively.
Conclusions: CNVs in regions encompassing important PCa genes were predictive of cancer significance and have the
potential to identify men with LRP PCa on needle biopsy who have IHRP PCa in their prostate gland.
Biography
Farhad Kosari’s interests are in the discovery and development of clinically relevant biomarkers for cancers. His domains of expertise are bioinformatics and
molecular biology particularly as related to the development of biomarker-based assays. His recent projects related to the identification of genomic abnormalities
that distinguish “indolent” from “significant” prostate cancers which is one of the most urgent needs in the clinical management of patients with PCa. His interests
also include neuroendocrine (NE) tumors of the lung including small cell lung cancers (SCLC) and adenocarcinomas with NE differentiation (ND-AD). Characterized
by the expression of ASCL1, ND-AD is a sizable subset of lung tumors that are largely understudied and underappreciated. Kosari’s group has recently discovered
the main drivers of ND-AD and is testing targeted therapies in patient-derived tumors. Furthermore, he has recently identified anti-tumor immunity as the key
determinant of survival in SCLC and is currently investigating the therapeutic implications of these findings.
Farhad Kosari, J Gastrointest Dig Syst 2018, Volume 8
DOI: 10.4172/2161-069X-C8-085