Frequent somatic mutations of GATA3 in non-BRCA1/BRCA2 familial breast tumors, but not in BRCA1-, BRCA2- or sporadic breast tumors

Heterozygous somatic mutations of the transcription factor, GATA-3, have recently been reported in approximately 5% breast of tumors unselected for family history. We sequenced the GATA-3 gene in 55 breast tumors from women with familial breast cancer, and found seven heterozygous somatic mutations, all in non-BRCA1/2 cases in which the frequency was 22%. In contrast, we found mutations of GATA-3 in only 4% of 81 sporadic tumors analysed. It is possible that GATA3 mutations occur earlier in the evolution of BRCAx tumors, compared to BRCA1, BRCA2 or sporadic tumors, and are therefore easier to detect by direct sequencing in the presence of some stromal contamination.

[1]  P. Romeo,et al.  Human GATA-3 trans-activation, DNA-binding, and nuclear localization activities are organized into distinct structural domains , 1994, Molecular and cellular biology.

[2]  R. Tibshirani,et al.  Repeated observation of breast tumor subtypes in independent gene expression data sets , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[3]  Charles M Perou,et al.  Somatic sequence alterations in twenty-one genes selected by expression profile analysis of breast carcinomas , 2007, Breast Cancer Research.

[4]  F. Grosveld,et al.  Transcription factor GATA‐3 alters pathway selection of olivocochlear neurons and affects morphogenesis of the ear , 2001, The Journal of comparative neurology.

[5]  K. Czene,et al.  No evidence that GATA3 rs570613 SNP modifies breast cancer risk , 2009, Breast Cancer Research and Treatment.

[6]  Nazneen Rahman,et al.  Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles , 2006, Nature Genetics.

[7]  Lester L. Peters,et al.  Genome-wide association study identifies novel breast cancer susceptibility loci , 2007, Nature.

[8]  J. Sambrook,et al.  Dominant negative ATM mutations in breast cancer families. , 2002, Journal of the National Cancer Institute.

[9]  S. Seal,et al.  PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene , 2007, Nature Genetics.

[10]  Marie-Liesse Asselin-Labat,et al.  Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation , 2007, Nature Cell Biology.

[11]  Shirley A. Miller,et al.  A simple salting out procedure for extracting DNA from human nucleated cells. , 1988, Nucleic acids research.

[12]  R. Strausberg,et al.  Mutation of GATA3 in human breast tumors , 2004, Oncogene.

[13]  C. Marshall,et al.  Multiple K-ras codon 12 mutations in cholangiocarcinomas demonstrated with a sensitive polymerase chain reaction technique. , 1991, Cancer research.

[14]  T. Tlsty.  Luminal cells GATA have it , 2007, Nature Cell Biology.

[15]  C. Perou,et al.  Common Genetic Variation in GATA-Binding Protein 3 and Differential Susceptibility to Breast Cancer by Estrogen Receptor α Tumor Status , 2007, Cancer Epidemiology Biomarkers & Prevention.

[16]  James Douglas Engel,et al.  Targeted disruption of the GATA3 gene causes severe abnormalities in the nervous system and in fetal liver haematopoiesis , 1995, Nature Genetics.

[17]  Nazneen Rahman,et al.  ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles , 2006, Nature Genetics.

[18]  R. Tibshirani,et al.  Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[19]  C. Perou,et al.  Common genetic variation in GATA-binding protein 3 and differential susceptibility to breast cancer by estrogen receptor alpha tumor status. , 2007, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[20]  T. Nielsen,et al.  GATA-3 Expression in Breast Cancer Has a Strong Association with Estrogen Receptor but Lacks Independent Prognostic Value , 2008, Cancer Epidemiology Biomarkers & Prevention.

[21]  P. Romeo,et al.  Structure and expression of the human GATA3 gene. , 1994, Genomics.

[22]  Zena Werb,et al.  GATA-3 Maintains the Differentiation of the Luminal Cell Fate in the Mammary Gland , 2006, Cell.

[23]  Q. Tong,et al.  Developmental biology: Cell fate in the mammary gland , 2007, Nature.

[24]  M. Simon,et al.  Gotta have GATA , 1995, Nature Genetics.

[25]  John L Hopper,et al.  Analysis of cancer risk and BRCA1 and BRCA2 mutation prevalence in the kConFab familial breast cancer resource , 2006, Breast Cancer Research.