BACKGROUND: Neuroblastoma (NB) is an important childhood cancer with a strong genetic component related to disease susceptibility. Approximately 1% of NB cases have a positive family history. Following a genome-wide linkage analysis and sequencing of candidate genes in the critical region, we identified ALK as the major familial NB gene. Dominant mutations in ALK are found in more than 50% of familial NB cases. However, in the families used for the linkage study, only about 50% of carriers of ALK mutations are affected by NB. METHODS: To test whether genetic variation may explain the reduced penetrance of the disease phenotype, we analyzed genome-wide genotype data in ALK mutation-positive families using a model-based linkage approach with different liability classes for carriers and non-carriers of ALK mutations. RESULTS: The region with the highest LOD score was located at chromosome 2p23-p24 and included the ALK locus under models of dominant and recessive inheritance. CONCLUSIONS: This finding suggests that variants in the non-mutated ALK gene or another gene linked to it may affect penetrance of the ALK mutations and risk of developing NB in familial cases.
BACKGROUND:Neuroblastoma (NB) is an important childhood cancer with a strong genetic component related to disease susceptibility. Approximately 1% of NB cases have a positive family history. Following a genome-wide linkage analysis and sequencing of candidate genes in the critical region, we identified ALK as the major familial NB gene. Dominant mutations in ALK are found in more than 50% of familial NB cases. However, in the families used for the linkage study, only about 50% of carriers of ALK mutations are affected by NB. METHODS: To test whether genetic variation may explain the reduced penetrance of the disease phenotype, we analyzed genome-wide genotype data in ALK mutation-positive families using a model-based linkage approach with different liability classes for carriers and non-carriers of ALK mutations. RESULTS: The region with the highest LOD score was located at chromosome 2p23-p24 and included the ALK locus under models of dominant and recessive inheritance. CONCLUSIONS: This finding suggests that variants in the non-mutated ALK gene or another gene linked to it may affect penetrance of the ALK mutations and risk of developing NB in familial cases.
Authors: J Randon; L Boulanger; J Marechal; M Garbarz; A Vallier; L Ribeiro; G Tamagnini; D Dhermy; J Delaunay Journal: Br J Haematol Date: 1994-11 Impact factor: 6.998
Authors: Yaël P Mossé; Marci Laudenslager; Luca Longo; Kristina A Cole; Andrew Wood; Edward F Attiyeh; Michael J Laquaglia; Rachel Sennett; Jill E Lynch; Patrizia Perri; Geneviève Laureys; Frank Speleman; Cecilia Kim; Cuiping Hou; Hakon Hakonarson; Ali Torkamani; Nicholas J Schork; Garrett M Brodeur; Gian P Tonini; Eric Rappaport; Marcella Devoto; John M Maris Journal: Nature Date: 2008-08-24 Impact factor: 49.962
Authors: Junne Kamihara; Franck Bourdeaut; William D Foulkes; Jan J Molenaar; Yaël P Mossé; Akira Nakagawara; Andreu Parareda; Sarah R Scollon; Kami Wolfe Schneider; Alison H Skalet; Lisa J States; Michael F Walsh; Lisa R Diller; Garrett M Brodeur Journal: Clin Cancer Res Date: 2017-07-01 Impact factor: 12.531