Mutation analysis of the SHFM1 gene in breast/ovarian cancer families.
OBJECTIVE
About 5-10 % of breast cancer is due to inherited disease predisposition. Currently known susceptibility genes such as BRCA1 and BRCA2 explain less than 25 % of familial aggregation of breast cancer, which suggests the involvement of additional genetic susceptibility. The SHFM1 [split hand/foot malformation (ectrodactyly) type 1] gene plays an important role in the regulation of gene transcription and cell proliferation and may be involved in the maintenance of genomic integrity. It is a potential candidate for being involved in heritable cancer susceptibility due to its biological function. The SHFM1 protein binds in mammalian cells to the longest conserved region of the BRCA2 protein and is required for BRCA2 stability and function, making a critical contribution to the BRCA2 function in mediating homologous recombination. Therefore, variants in the SHFM1 gene could affect the BRCA2 functionality and be associated with the familial breast/ovarian carcinogenesis.


METHODS
We have screened the entire coding region and splice junctions of SHFM1 in affected index cases from 369 Spanish breast/ovarian cancer families for germ line defects, using direct sequencing.


RESULTS
Mutation analysis revealed seven different sequence changes. Based on the in silico analyses of these sequence alterations, as well as their occurrence in cases and controls, none of them, however, were predicted to be pathogenic or associated with cancer susceptibility.


CONCLUSIONS
To our knowledge, this is the most comprehensive study reporting the mutation screening of the SHFM1 gene in familial breast/ovarian cancer cases. No evidence for the association with breast/ovarian cancer was observed.
Oncogenetics Laboratory, Vall d'Hebron Institute of Oncology, Universitat Autonoma de Barcelona, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain. sbonache@vhebron.net
Sandra
S
Bonache
Miguel
M
de la Hoya
Sara
S
Gutierrez-Enriquez
Anna
A
Tenés
Miriam
M
Masas
Judith
J
Balmaña
Orland
O
Diez
D001943:Breast Neoplasms / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000453:epidemiology / Q000235:genetics; D002277:Carcinoma / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D009378:Neoplasms, Multiple Primary / Q000453:epidemiology / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D046988:Proteasome Endopeptidase Complex / Q000235:genetics*
C484606:SEM1 protein, human; D046988:Proteasome Endopeptidase Complex