The Icelandic founder mutation BRCA2 999del5: analysis of expression

Breast Cancer Research : BCR
Evgenia K MikaelsdottirThorunn Rafnar

Abstract

A founder mutation in the BRCA2 gene (BRCA2 999del5) accounts for 7-8% of female breast cancers and for 40% of male breast cancers in Iceland. If expressed, the mutant gene would encode a protein consisting of the first 256 amino acids of the BRCA2 protein. The purpose of this study was to determine whether this mutant protein is produced in heterozygous individuals and, if so, what might be the functional consequences of mutant protein production. The presence of BRCA2 999del5 transcripts in fibroblasts from heterozygous individuals was assayed by cDNA synthesis and sequencing. The potential protein-coding portion of BRCA2 999del5 was cloned into the pIND(SP1)/V5-His vector and expressed in COS7 cells. The presence of the mutant protein in cell lysates from heterozygous fibroblasts and from COS7 cells was tested by a number of methods including immunoprecipitation, affinity purification with nickel-coated agarose beads, Western blotting and ELISA, using antibodies to the N-terminal end of BRCA2, antiserum specific for the 16 nonrelevant amino acids at the carboxyl end and antibodies to fusion partners of recombinant proteins. The frequency of the BRCA2 999del5 transcript in heterozygous fibroblasts was about one-fifth of the w...Continue Reading

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Citations

Nov 29, 2012·Journal of Genetic Counseling·Janice L BerlinerTodd Tillmanns
Aug 7, 2009·Human Molecular Genetics·Antonis C AntoniouUNKNOWN CIMBA
Sep 6, 2011·Human Molecular Genetics·David G CoxUNKNOWN Consortium of Investigators of Modifiers of BRCA1/2
Jan 19, 2006·Journal of the National Cancer Institute·Laufey TryggvadottirJorunn E Eyfjörd
Jun 15, 2007·Journal of the National Cancer Institute·Laufey TryggvadóttirHrafn Tulinius
Jan 25, 2008·Annals of Human Genetics·F MarroniG Bevilacqua
Jun 29, 2007·Annals of Surgical Oncology·Tari A KingJeff Boyd
Jan 16, 2013·Journal of Epidemiology·Wenming CaoJi-Cheng Li
Feb 2, 2006·In Vitro Cellular & Developmental Biology. Animal·Agla J Rubner FridriksdottirHelga M Ogmundsdottir
Nov 11, 2014·Journal of Surgical Oncology·Thereasa A RichBanu Arun
Dec 3, 2014·Experimental Cell Research·Hyunsook Lee
May 17, 2018·Journal of the National Cancer Institute·Shailja Pathania, Judy E Garber
May 17, 2018·Journal of the National Cancer Institute·Thorunn RafnarKari Stefansson
May 22, 2019·Human Mutation·Tara M FriebelTimothy R Rebbeck
Feb 16, 2018·Human Mutation·Timothy R RebbeckKatherine L Nathanson
Jul 9, 2005·Mutation Research·Jorunn Erla Eyfjord, Sigridur Klara Bodvarsdottir

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Methods Mentioned

BETA
electrophoresis
transfection
transfections
affinity purification
ELISA
FCS

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