Association of biallelic BRCA2/FANCD1 mutations with spontaneous chromosomal instability and solid tumors of childhood

Betsy Hirsch, Akiko Shimamura, Lisa Moreau, Shari Baldinger, Maha Hag-Alshiekh, Bruce Bostrom, Susan Sencer, Alan D. D'Andrea

Research output: Contribution to journalArticlepeer-review

135 Scopus citations

Abstract

The clinical, cytogenetic, and molecular findings of 2 Fanconi anemia (FA) subtype D1 kindreds, initially identified through a young child with a solid tumor (medullobastoma, Wilms tumor), are described. Each kindred subsequently had a second affected child; one developed Wilms tumor followed by a medulloblastoma, and the other developed T-lineage acute lymphoblastic leukemia. Cytogenetic studies revealed an unusually high spontaneous chromosome aberration rate, contrasting with other FA subtypes. Molecular analysis revealed biallelic BRCA2/FANCD1 mutations. The patients did not exhibit bone marrow failure. Our studies suggest that the D1 subtype represents a severe end of the cytogenetic spectrum within FA, consistent with a critical downstream role of BRCA2 in the FA pathway. Furthermore, this FA sub-group may be preferentially associated with an increased predisposition to solid tumors in early childhood. Recognition of this constellation of findings has significant implications for medical management and genetic counseling of FA families.

Original languageEnglish (US)
Pages (from-to)2554-2559
Number of pages6
JournalBlood
Volume103
Issue number7
DOIs
StatePublished - Apr 1 2004

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