title: Germline ATM mutational analysis in BRCA1/BRCA2 negative hereditary breast cancer families by MALDI-TOF mass spectrometry.
abstract: Biallelic inactivation of ATM gene causes the rare autosomal recessive disorder Ataxia-telangiectasia (A-T). Female relatives of A-T patients have a two-fold higher risk of developing breast cancer (BC) compared with the general population. ATM mutation carrier identification is laborious and expensive, therefore, a more rapid and directed strategy for ATM mutation profiling is needed. We designed a case-control study to determine the prevalence of 32 known ATM mutations causing A-T in Spanish population in 323 BRCA1/BRCA2 negative hereditary breast cancer (HBC) cases and 625 matched Spanish controls. For the detection of the 32 ATM mutations we used the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry technique. We identified one patient carrier of the c.8264_8268delATAAG ATM mutation. This mutation was not found in the 625 controls. These results suggest a low frequency of these 32 A-T causing mutations in the HBC cases in our population. Further case-control studies analyzing the entire coding and flanking sequences of the ATM gene are warranted in Spanish BC patients to know its implication in BC predisposition.
authors: High Risk and Cancer Prevention Unit, Vall d'Hebron Institute of Oncology, University Hospital Vall d'Hebron, P. Vall d'Hebron 119-129, 08035 Barcelona, Spain. bgrana@vhebron.net
authors: B
authors: B
authors: Graña
authors: L
authors: L
authors: Fachal
authors: E
authors: E
authors: Darder
authors: J
authors: J
authors: Balmaña
authors: T
authors: T
authors: Ramón Y Cajal
authors: I
authors: I
authors: Blanco
authors: A
authors: A
authors: Torres
authors: C
authors: C
authors: Lázaro
authors: O
authors: O
authors: Diez
authors: C
authors: C
authors: Alonso
authors: M
authors: M
authors: Santamariña
authors: A
authors: A
authors: Velasco
authors: A
authors: A
authors: Teulé
authors: A
authors: A
authors: Lasa
authors: A
authors: A
authors: Blanco
authors: A
authors: A
authors: Izquierdo
authors: J
authors: J
authors: Borràs
authors: S
authors: S
authors: Gutiérrez-Enríquez
authors: A
authors: A
authors: Vega
authors: J
authors: J
authors: Brunet
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D004247:DNA / Q000032:analysis / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D004247:DNA; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases