Genomics in the Scientific Literature [13] - Cancer

Genomics in the Scientific Literature
Topics in the Scientific Literature

Cancer

1. Germline copy number variation and cancer risk
Kuiper RP, et al.
Curr Opin Genet Dev 2010 Apr

Curr Opin Genet Dev. 2010 Apr 6. [Epub ahead of print]

Germline copy number variation and cancer risk.
Kuiper RP, Ligtenberg MJ, Hoogerbrugge N, Geurts van Kessel A.

Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life Sciences, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.

Abstract
The human genome is subject to substantial structural variation, including copy number variation (CNV). Constitutional CNVs may either represent benign polymorphic variants or be associated with disease, including cancer predisposition. Rare nonpolymorphic CNVs, that is DNA lesions that result in gene deletions, inversions, and/or fusions, may be responsible for a high cancer risk. In addition, we previously elucidated a mechanism by which CNV-based transcriptional read-through mediates inactivation of a neighboring gene through in cis hypermethylation of its promoter. This novel mechanism explains the etiology of a recurrent and strongly inherited tissue-restricted epimutation. Recently, we obtained supporting evidence for such a CNV-associated scenario, suggesting that it may be more prevalent than previously thought. We expect that copy number profiling in unexplained high-risk families will lead to the discovery of additional cancer-predisposing genes and/or mechanisms. Copyright © 2010 Elsevier Ltd. All rights reserved.

PMID: 20381334 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20381334?dopt=Abstract



2. Uridine 5'-diphospho-glucuronosyltransferase genetic polymorphisms and response to cancer chemotherapy
Ramirez J, et al.
Future Oncol 2010 Apr;6(4):563-85

Future Oncol. 2010 Apr;6(4):563-85.

Uridine 5'-diphospho-glucuronosyltransferase genetic polymorphisms and response to cancer chemotherapy.
Ramírez J, Ratain MJ, Innocenti F.

Department of Medicine, The University of Chicago, 5841 S. Maryland Avenue, MC2115, Chicago, IL 60637, USA. jramirez@medicine.bsd.uchicago.edu

Abstract
Pharmacogenetics aims to elucidate how genetic variation affects the efficacy and side effects of drugs, with the ultimate goal of personalizing medicine. Clinical studies of the genetic variation in the uridine 5'-diphosphoglucuronosyltransferase gene have demonstrated how reduced-function allele variants can predict the risk of severe toxicity and help identify cancer patients who could benefit from reduced-dose schedules or alternative chemotherapy. Candidate polymorphisms have also been identified in vitro, although the functional consequences of these variants still need to be tested in the clinical setting. Future approaches in uridine 5'-diphosphoglucuronosyltransferase pharmacogenetics include genetic testing prior to drug treatment, genotype-directed dose-escalation studies, study of genetic variation at the haplotype level and genome-wide studies.

PMID: 20373870 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/20373870?dopt=Abstract