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Development of primary early-onset colorectal cancers due to biallelic mutations of the FANCD1/BRCA2 gene.
Degrolard-Courcet, Emilie; Sokolowska, Joanna; Padeano, Marie-Martine; Guiu, Séverine; Bronner, Myriam; Chery, Carole; Coron, Fanny; Lepage, Côme; Chapusot, Caroline; Loustalot, Catherine; Jouve, Jean-Louis; Hatem, Cyril; Ferrant, Emmanuelle; Martin, Laurent; Coutant, Charles; Baurand, Amandine; Couillault, Gérard; Delignette, Alexandra; El Chehadeh, Salima; Lizard, Sarab; Arnould, Laurent; Fumoleau, Pierre; Callier, Patrick; Mugneret, Francine; Philippe, Christophe; Frebourg, Thierry; Jonveaux, Philippe; Faivre, Laurence.
Afiliação
  • Degrolard-Courcet E; Service d'Anatomie et Cytologie Pathologiques, Pole Technique et biologie CHU Dijon, Dijon, France.
  • Sokolowska J; Laboratoire de Génétique et INSERM U-954, CHU Nancy, Université de Lorraine, Nancy, France.
  • Padeano MM; Département de Chirurgie, Centre de lutte anti-cancereux Georges François Leclerc, Dijon, France.
  • Guiu S; Département d'oncologie médicale, Centre de lutte anti-cancereux Georges François Leclerc, Dijon, France.
  • Bronner M; Laboratoire de Génétique et INSERM U-954, CHU Nancy, Université de Lorraine, Nancy, France.
  • Chery C; Laboratoire de Génétique et INSERM U-954, CHU Nancy, Université de Lorraine, Nancy, France.
  • Coron F; Centre de Génétique, Hôpital d'Enfants, CHU Dijon et Université de bourgogne, Dijon, France.
  • Lepage C; Service d' Hepato-gastro-enterologie, CHU "Bocage Central", Dijon, France.
  • Chapusot C; Service d'Anatomie et Cytologie Pathologiques, Pole Technique et biologie CHU Dijon, Dijon, France.
  • Loustalot C; Département de Chirurgie, Centre de lutte anti-cancereux Georges François Leclerc, Dijon, France.
  • Jouve JL; Service d' Hepato-gastro-enterologie, CHU "Bocage Central", Dijon, France.
  • Hatem C; Hepato-gastro-entérologie, Clinique Drevon, Dijon, France.
  • Ferrant E; Service d'Hématologie Clinique, Hôpital d'Enfants, CHU Dijon, Dijon, France.
  • Martin L; Service d'Anatomie et Cytologie Pathologiques, Pole Technique et biologie CHU Dijon, Dijon, France.
  • Coutant C; Département de Chirurgie, Centre de lutte anti-cancereux Georges François Leclerc, Dijon, France.
  • Baurand A; Centre de Génétique, Hôpital d'Enfants, CHU Dijon et Université de bourgogne, Dijon, France.
  • Couillault G; Service de Pédiatrie 1, Hôpital d'Enfants, CHU Dijon, Dijon, France.
  • Delignette A; Service de Radiologie, Centre de lutte anti-cancereux Georges François Leclerc, Dijon, France.
  • El Chehadeh S; Centre de Génétique, Hôpital d'Enfants, CHU Dijon et Université de bourgogne, Dijon, France.
  • Lizard S; Biologie Moléculaire, Centre de lutte anti-cancereux Georges François Leclerc, Dijon, France.
  • Arnould L; Anatomopathologie, Centre de lutte anti-cancereux Georges François Leclerc, Dijon, France.
  • Fumoleau P; Département d'oncologie médicale, Centre de lutte anti-cancereux Georges François Leclerc, Dijon, France.
  • Callier P; Service de Cytogénétique, Pole Technique et biologie, CHU Dijon, Dijon, France.
  • Mugneret F; Service de Cytogénétique, Pole Technique et biologie, CHU Dijon, Dijon, France.
  • Philippe C; Laboratoire de Génétique et INSERM U-954, CHU Nancy, Université de Lorraine, Nancy, France.
  • Frebourg T; Inserm U1079 et Département de Génétique, CHU de Rouen, France.
  • Jonveaux P; Laboratoire de Génétique et INSERM U-954, CHU Nancy, Université de Lorraine, Nancy, France.
  • Faivre L; Centre de Génétique, Hôpital d'Enfants, CHU Dijon et Université de bourgogne, Dijon, France.
Eur J Hum Genet ; 22(8): 979-87, 2014 Aug.
Article em En | MEDLINE | ID: mdl-24301060
Fanconi anaemia (FA) is characterized by progressive bone marrow failure, congenital anomalies, and predisposition to malignancy. In a minority of cases, FA results from biallelic FANCD1/BRCA2 mutations that are associated with early-onset leukaemia and solid tumours. Here, we describe the clinical and molecular features of a remarkable family presenting with multiple primary colorectal cancers (CRCs) without detectable mutations in genes involved in the Mendelian predisposition to CRCs. We unexpectedly identified, despite the absence of clinical cardinal features of FA, a biallelic mutation of the FANCD1/BRCA2 corresponding to a frameshift alteration (c.1845_1846delCT, p.Asn615Lysfs*6) and a missense mutation (c.7802A>G, p.Tyr2601Cys). The diagnosis of FA was confirmed by the chromosomal analysis of lymphocytes. Reverse transcriptase (RT)-PCR analysis revealed that the c.7802A>G BRCA2 variation was in fact a splicing mutation that creates an aberrant splicing donor site and results partly into an aberrant transcript encoding a truncated protein (p.Tyr2601Trpfs*46). The atypical FA phenotype observed within this family was probably explained by the residual amount of BRCA2 with the point mutation c.7802A>G in the patients harbouring the biallelic FANCD1/BRCA2 mutations. Although this report is based in a single family, it suggests that CRCs may be part of the tumour spectrum associated with FANCD1/BRCA2 biallelic mutations and that the presence of such mutations should be considered in families with CRCs, even in the absence of cardinal features of FA.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Idade de Início / Proteína BRCA2 / Alelos / Mutação Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Adult / Female / Humans Idioma: En Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Idade de Início / Proteína BRCA2 / Alelos / Mutação Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Adult / Female / Humans Idioma: En Ano de publicação: 2014 Tipo de documento: Article