Abstract
Mutations in BRCA1 and BRCA2 genes confer a high risk of breast and ovarian cancer. As such, their identification is essential to reduce the risk of disease in healthy carriers, as well as in carriers who have already developed the disease because they are at increased risk for a second malignancy; moreover, noncarriers of BRCA1 and BRCA2 mutated families can be spared anxiety and unnecessary medical interventions. A number of problems, including large gene size, complex mutational spectra and genetic heterogeneity of the disease, however, make genetic testing labor intensive and often inconclusive. We devised a new mutation detection strategy called AGE (allele-specific gene expression) analysis that relies on the detection of a "functional effect" of the mutation at the RNA level known as "nonsense-mediated RNA decay," thus avoiding several of the problems of BRCA1 and BRCA2 genetic testing. In particular, (i) AGE analysis discriminates among the predisposing genes and identifies mutation carriers with a single RT-PCR reaction; (ii) it relies on the effect of truncating mutations, which represent the large majority of cases and thus identifies mutation carriers regardless of the specific genomic alteration; and (iii) it is sp...Continue Reading
References
Jun 1, 1995·Nature Genetics·F B HogervorstH Meijers-Heijboer
Dec 1, 1994·Nature Genetics·L S FriedmanM C King
Jun 1, 1996·Human Molecular Genetics·F DurocherJ Simard
Oct 1, 1996·Genome Research·C A HeidP M Williams
Dec 1, 1996·Nature Genetics·J G HaciaF S Collins
Feb 1, 1997·Human Molecular Genetics·A M DunningB A Ponder
Mar 1, 1997·Human Molecular Genetics·A P ShuberK W Klinger
Nov 14, 1997·Nature Genetics·A Petrij-BoschP Devilee
Apr 29, 1998·American Journal of Human Genetics·D FordM Zelada-Hedman
Jun 23, 1998·American Journal of Human Genetics·F H FodorC M Eng
Jun 30, 1998·Trends in Biochemical Sciences·E Nagy, L E Maquat
Aug 6, 1999·Oncogene·M MontagnaE D'Andrea
Sep 2, 1999·Human Molecular Genetics·P A Frischmeyer, H C Dietz
Oct 12, 1999·Breast Cancer Research and Treatment·M FedericoV Silingardi
Jan 25, 2000·Genomics·T WagnerP Oefner
May 10, 2000·Nature Biotechnology·R FavisF Barany
Aug 16, 2000·Proceedings of the National Academy of Sciences of the United States of America·T KainuH Nevanlinna
Sep 1, 2000·Seminars in Cancer Biology·B ArverA Lindblom
Sep 21, 2000·BioTechniques·P RossL A Haff
Jan 11, 2000·Human Mutation·R Shiri-SverdlovE Friedman
Jan 3, 2001·American Journal of Human Genetics·J CuiJ L Hopper
Citations
Feb 28, 2003·Cancer Genetics and Cytogenetics·Simona AgataMarco Montagna
Aug 7, 2009·Human Molecular Genetics·Antonis C AntoniouUNKNOWN CIMBA
Sep 24, 2010·Annals of Human Genetics·Mauro Santibanez KorefJohn Burn
Jun 15, 2007·BMC Medical Genetics·Petra VasickovaLenka Foretova
Mar 17, 2004·Human Mutation·Isabelle TournierMario Tosi
May 12, 2016·Journal of Translational Medicine·Jason C HallJohn A Copland
Aug 10, 2007·Acta Biochimica Et Biophysica Sinica·Jingshu HuangSiwen Jiang