TY - JOUR
T1 - Deletion of one copy of the p16(INK4) tumor suppressor gene is implicated as a predisposing factor in pediatric leukemia
AU - Carter, T.L.
AU - Terry, P.
AU - Gottardo, N.
AU - Baker, D.L.
AU - Kees, Ursula
AU - Watt, Paul
PY - 2004
Y1 - 2004
N2 - The p16(INK4A) tumor suppressor gene is frequently disrupted by mutation or deletion in a wide range of cancer types, ranging from leukemia to cancers of the bladder, skin, lung, liver, and spleen. We have previously shown that deletion of at least one copy of the p16(INK4A) gene is associated with an increased risk of relapse in pediatric leukemia. Our data suggest that hemizygous p16(INK4A) deletion may be constitutional, conferring susceptibility to leukemia. Confirmation of this association is worthy of a larger study. Data from primary leukemia specimens are also presented here which examined the possibility that the remaining allele of the gene was inactivated by another mechanism such as mutation or was silenced by methylation. These possibilities were formally excluded in a case of hemizygous loss of the p16(INK4A) gene in leukemia, establishing that in this case the p16(INK4A) deletion was either semidominant or fully haploinsufficient for relapse susceptibility in this disease. Implementation of high throughput methods such as those used here for detecting hemizygous loss of tumor suppressor genes will become increasingly important for molecular diagnosis of cancer. This is particularly true for the emerging class of tumor suppressor genes where deletion of one allele is sufficient to confer cancer susceptibility or poor prognosis with standard treatment. (C) 2004 Published by Elsevier Inc.
AB - The p16(INK4A) tumor suppressor gene is frequently disrupted by mutation or deletion in a wide range of cancer types, ranging from leukemia to cancers of the bladder, skin, lung, liver, and spleen. We have previously shown that deletion of at least one copy of the p16(INK4A) gene is associated with an increased risk of relapse in pediatric leukemia. Our data suggest that hemizygous p16(INK4A) deletion may be constitutional, conferring susceptibility to leukemia. Confirmation of this association is worthy of a larger study. Data from primary leukemia specimens are also presented here which examined the possibility that the remaining allele of the gene was inactivated by another mechanism such as mutation or was silenced by methylation. These possibilities were formally excluded in a case of hemizygous loss of the p16(INK4A) gene in leukemia, establishing that in this case the p16(INK4A) deletion was either semidominant or fully haploinsufficient for relapse susceptibility in this disease. Implementation of high throughput methods such as those used here for detecting hemizygous loss of tumor suppressor genes will become increasingly important for molecular diagnosis of cancer. This is particularly true for the emerging class of tumor suppressor genes where deletion of one allele is sufficient to confer cancer susceptibility or poor prognosis with standard treatment. (C) 2004 Published by Elsevier Inc.
U2 - 10.1016/j.bbrc.2004.04.104
DO - 10.1016/j.bbrc.2004.04.104
M3 - Article
C2 - 15147949
VL - 318
SP - 852
EP - 855
JO - Biochemistry Biophysics Research Communications
JF - Biochemistry Biophysics Research Communications
SN - 0006-291X
IS - 4
ER -