Molecular anatomy of chromosome 7q deletions in myeloid neoplasms: Evidence for multiple critical loci

Abstract

Complete or partial deletions of the long arm of chromosome 7 (7q-and -7) are nonrandom abnormalities seen in primary and therapy-induced myelodysplasia (MDS) and acute myelogenous leukemia (AML). Monosomy 7, occurring as the sole cytogenetic anomaly in a small but significant number of cases, may denote a dominant mechanism involving critical tumor suppressor gene(s). We have determined the extent of allele loss in cytogenetically prescreened MDS and AML patients for microsatellite markers from chromosome 7q22 and 7q31. Whereas >80% of these cases revealed allele loss for the entire region, a rare case of the 7q-chromosome showed allele loss for only the proximal 7q31.1 loci f lanked by the markers D7S486 and D7S2456, and a case of monosomy 7 revealed allele loss for loci at both 7q31 and 7q22 with retention of sequences between these sets of loci. Furthermore, a case of AML with no cytogenetic anomaly of chromosome 7 revealed a submicroscopic allelic imbalance for a third distal locus, D7S677. These findings suggest the presence of three distinct critical loci that may contribute alone or in combination to the evolution of MDS and AML. The data also provide molecular evidence for unbalanced translocation with noncontiguous deletions, as an alternate mechanism underlying monosomy 7.

Secondary acute myelogenous leukemia and myelodysplasia without abnormalities of chromosome 11q23 following treatment of acute leukemia with topoisomerase II-based chemotherapy

“…Further molecular studies by other authors supports the presence of multiple critical loci on chromosome 7 leading to the development of MDS and AML. 27,28 In the current study six patients developed new abnormalities involving chromosome arm 7q. This abnormality resolved spontaneously in two patients but progressed to AML in four other patients.…”

Deletions of PURA, at 5q31, and PURB, at 7p13, in myelodysplastic syndrome and progression to acute myelogenous leukemia

“…16 Similarly, no tumor suppressor genes have yet been identified at deleted loci on chromosome 7. The possibility has been noted that tumor suppressor genes are present at more than one site on the long arms of chromosome 7, 17 as deletions of 7q are more frequently seen in MDS patients than deletions in 7p. 1 On the other hand, deletions of 7p are seen in a significant number of cases, 1,18 and thus it is conceivable that the high prevalence of monosomy 7 reflects the critical nature of multiple genes on both the short and long arms of chromosome 7.…”

Causality of myelodysplasia and acute myeloid leukemia and their genetic abnormalities

“…Chromosome damage which may lead to deletions or total chromosomal loss is frequent following chemotherapy with alkylating agents, and because two different deletions of the long arm of a chromosome 5 or a chromosome 7 are sometimes observed in cytogenetically unrelated clones in the same patient, the chromosome defects most likely are secondary and potentiate or activate the effects of other more important preclinical genetic changes 23 (Figure 1a and c). Inactivated recessive genes on the remaining normal chromosome 5 or 7 have been searched for, so far without success, [24][25][26][27][28] for which reason haploinsufficiency must also be considered.…”