TY - JOUR
T1 - Molecular variants of the ATM gene in Hodgkin's disease in children
AU - Liberzon, E.
AU - Avigad, S.
AU - Yaniv, I.
AU - Stark, B.
AU - Avrahami, G.
AU - Goshen, Y.
AU - Zaizov, R.
N1 - Funding Information:
This research was funded in part by the Israel Cancer Association through a donation from Mr and Mrs Peter Brown, Florida, in memory of Eric Brown, and by The Josefina Maus and Gabriela Cesarman Maus Chair for Pediatric Hematology Oncology (RZ). Human DNA samples were obtained from The National Laboratory for the Genetics of Israeli Populations at Tel-Aviv University, Israel. This work was performed in partial fulfillment of the requirements for the PhD degree of Ella Liberzon, Sackler School of Medicine, Tel Aviv University, Israel.
PY - 2004/1/26
Y1 - 2004/1/26
N2 - Ataxia telangiectasia is an autosomat recessive disease with a striking predisposition of lymphoid malignancies. ATM mutations have been reported in adult sporadic lymphoma and leukaemia. The aim of this study was to investigate the possible involvement of the ATM gene in the carcinogenesis of Hodgkin disease in children. Tumours were obtained from 23 patients and were subjected to mutation screening and loss of heterozygosity analysis. Eight base substitutions were identified in seven patients. Of them, Y54Y, a silent change, was observed in two patients and a known polymorphism, D1853N, in three patients. Of the other two patients, one harboured a combined genotype P604S/F1463C, identified previously in two patients with Hodgkin lymphoma, and the other a novel missense mutation, V595A. The alterations were present in the germ line, and both had a more aggressive disease. In all, 100 matched normal ethnic controls were screened for these mutations and P604S/F1463C was identified in one healthy control. Loss of heterozygosity was identified in four patients and in three of them it was located centromeric to the ATM gene, and, in one, it spanned a large region, indicating the involvement of other tumour-suppressor genes in this disease. Missense variants of the ATM gene are a rare event in childhood Hodgkin disease.
AB - Ataxia telangiectasia is an autosomat recessive disease with a striking predisposition of lymphoid malignancies. ATM mutations have been reported in adult sporadic lymphoma and leukaemia. The aim of this study was to investigate the possible involvement of the ATM gene in the carcinogenesis of Hodgkin disease in children. Tumours were obtained from 23 patients and were subjected to mutation screening and loss of heterozygosity analysis. Eight base substitutions were identified in seven patients. Of them, Y54Y, a silent change, was observed in two patients and a known polymorphism, D1853N, in three patients. Of the other two patients, one harboured a combined genotype P604S/F1463C, identified previously in two patients with Hodgkin lymphoma, and the other a novel missense mutation, V595A. The alterations were present in the germ line, and both had a more aggressive disease. In all, 100 matched normal ethnic controls were screened for these mutations and P604S/F1463C was identified in one healthy control. Loss of heterozygosity was identified in four patients and in three of them it was located centromeric to the ATM gene, and, in one, it spanned a large region, indicating the involvement of other tumour-suppressor genes in this disease. Missense variants of the ATM gene are a rare event in childhood Hodgkin disease.
KW - ATM
KW - Hodgkin lymphoma
KW - Mutations
UR - http://www.scopus.com/inward/record.url?scp=1342301545&partnerID=8YFLogxK
U2 - 10.1038/sj.bjc.6601522
DO - 10.1038/sj.bjc.6601522
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AN - SCOPUS:1342301545
SN - 0007-0920
VL - 90
SP - 522
EP - 525
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 2
ER -
