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BARD1 homozygous deletion, a possible alternative to BRCA1 mutation in basal breast cancer
Author(s) -
Sabatier Renaud,
Adélaïde José,
Finetti Pascal,
Ferrari Anthony,
Huiart Laetitia,
Sobol Hagay,
Chaffanet Max,
Birnbaum Daniel,
Bertucci François
Publication year - 2010
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20822
Subject(s) - biology , genetics , mutation , fanca , germline mutation , germline , gene , comparative genomic hybridization , palb2 , cancer research , microbiology and biotechnology , dna repair , chromosome , fanconi anemia
Hereditary breast cancers (BCs) are incompletely explained by BRCA genes abnormalities, as ∼70% of them are not associated with known genetic alterations. Array‐based comparative genomic hybridization (aCGH) of tumors provides an opportunity for identifying new BC susceptibility genes. By analyzing our database of high‐resolution aCGH profiles of 330 BCs, we identified a case with homozygous deletion of the entire BARD1 gene. The BARD1 ‐deleted case displayed a familial history of BC and other clinico‐pathological features of BRCAness, and a 17% probability of BRCA1/2 mutation. Analysis of constitutional DNA showed a BARD1 germline heterozygous deletion without BRCA1/2 mutation. Gene expression analysis using DNA microarrays classified the tumor as basal‐like, with very low BARD1 and ID4 expression, but high expression of BRCA1, RAD51 , PARP1 , CHEK1 , and FANCA . The tumor displayed a BRCA1 ‐mutated expression profile. This is the first report of a non‐ BRCA1/2 ‐mutated BC with somatic homozygous and germ‐line heterozygous deletion of the entire BARD1 gene. This observation suggests that BARD1 might be a BC susceptibility gene that follows the Knudson rule. Identification of BARD1 deletion could have clinical applications including screening for hereditary forms. © 2010 Wiley‐Liss, Inc.