RESUMO
A subset of human cancer syndromes result from inherited defects in genes responsible for DNA repair. During the past few years, discoveries concerning the intersection of certain DNA repair processes have increased our understanding of how the disruption of specific DNA repair mechanisms leads to genomic instability and tumorigenesis. This review focuses on the human genes MUTYH, BRCA2/FANCD1, and BLM.
Assuntos
Reparo do DNA/genética , Síndromes Neoplásicas Hereditárias/genética , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Proteína BRCA2/genética , Proteína BRCA2/metabolismo , Síndrome de Bloom/genética , Síndrome de Bloom/metabolismo , Neoplasias Colorretais/genética , DNA Glicosilases/genética , DNA Glicosilases/metabolismo , DNA Helicases/genética , DNA Helicases/metabolismo , Anemia de Fanconi/genética , Anemia de Fanconi/metabolismo , Humanos , Modelos Genéticos , Mutação , Síndromes Neoplásicas Hereditárias/metabolismo , RecQ HelicasesRESUMO
Persons with the autosomal recessive disorder Bloom syndrome are predisposed to cancers of many types due to loss-of-function mutations in the BLM gene, which encodes a recQ-like helicase. Here we show that mice heterozygous for a targeted null mutation of Blm, the murine homolog of BLM, develop lymphoma earlier than wild-type littermates in response to challenge with murine leukemia virus and develop twice the number of intestinal tumors when crossed with mice carrying a mutation in the Apc tumor suppressor. These observations indicate that Blm is a modifier of tumor formation in the mouse and that Blm haploinsufficiency is associated with tumor predisposition, a finding with important implications for cancer risk in humans.