TY - JOUR
T1 - Deletions of chromosome 5q13.3 and 17p loci cooperate in myeloid neoplasms
AU - Castro, Patricia D.
AU - Liang, Jan C.
AU - Nagarajan, Lalitha
PY - 2000/3/15
Y1 - 2000/3/15
N2 - Nonrandom interstitial deletions and monosomy of chromosomes 5, 7, and 17 in refractory myelodysplasia (MDS) and acute myelogenous leukemia (AML) suggest a multistep pathway that culminates in aggressive clinical course. Because cytogenetic studies frequently identify chromosome 5 and 17 deletions within a single clone, we searched for allele loss for 5q loci and TP53 gene mutations In the same leukemic samples. Cosegregating deletions of chromosomes 5 and 17 were found to specifically include the 5q13.3 interval between the loci D5S672 and D5S620/D5S626, a locus hypothesized to harbor a tumor suppressor gene and the TP53 gene on 17p. A rare patient with secondary refractory MDS and an unbalanced translocation [der(5;17)], which resulted in deletions of the 5q13.3-qter and 17p loci, provided clues on the sequence of genetic alterations. Serial molecular analysis of this patient revealed a dysplastic clone with der(5;17), which gave rise to a leukemic clone on acquiring an inactivating mutation of TP53. Our findings are consistent with functional cooperation between a putative tumor suppressor gene at 5q13.3 that contribute s toward the progression of early stages of MDS, and the TP53 gene when mutated, causes transformation to AML. (C) 2000 by The American Society of Hematology.
AB - Nonrandom interstitial deletions and monosomy of chromosomes 5, 7, and 17 in refractory myelodysplasia (MDS) and acute myelogenous leukemia (AML) suggest a multistep pathway that culminates in aggressive clinical course. Because cytogenetic studies frequently identify chromosome 5 and 17 deletions within a single clone, we searched for allele loss for 5q loci and TP53 gene mutations In the same leukemic samples. Cosegregating deletions of chromosomes 5 and 17 were found to specifically include the 5q13.3 interval between the loci D5S672 and D5S620/D5S626, a locus hypothesized to harbor a tumor suppressor gene and the TP53 gene on 17p. A rare patient with secondary refractory MDS and an unbalanced translocation [der(5;17)], which resulted in deletions of the 5q13.3-qter and 17p loci, provided clues on the sequence of genetic alterations. Serial molecular analysis of this patient revealed a dysplastic clone with der(5;17), which gave rise to a leukemic clone on acquiring an inactivating mutation of TP53. Our findings are consistent with functional cooperation between a putative tumor suppressor gene at 5q13.3 that contribute s toward the progression of early stages of MDS, and the TP53 gene when mutated, causes transformation to AML. (C) 2000 by The American Society of Hematology.
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U2 - 10.1182/blood.v95.6.2138
DO - 10.1182/blood.v95.6.2138
M3 - Article
C2 - 10706886
AN - SCOPUS:0034654412
SN - 0006-4971
VL - 95
SP - 2138
EP - 2143
JO - Blood
JF - Blood
IS - 6
ER -