The underlying molecular defect that produces the isolated i(17q) is unknown: breakage of the proximal p arm (17p11.2) with rejoining of both centromere-containing chromatids and subsequent inactivation of one centromere; breakpoints could involve important genetic material whose disruption could result in oncogene or tumor suppression gene deregulation.
In understanding the specific i(17q) phenotype, loss of genes localized on 17p were suggested as p53 (17p13.1); a direct correlation between p53 loss and PHH neutrophils was found in a series of MDS and AML with 17p- syndrome. However, Fioretos et al. assessed TP53 mutations in 5 Philadelphia negative myeloid neoplasms with isolated isochromosome.
17q by sequencing, and found no mutation in all 5 cases. Similarly, none of the 14 cases assessed in another series of patients demonstrated TP53 mutation. These results suggest that there is no association between isochromosome 17q and TP53 mutations, and that another oncogene(s) at 17q and/or tumor suppressor gene(s) at 17p may play an important role in the pathogenesis of isochromosome 17q-associated myeloid neoplasms. The presence of a moderate apoptotic rate also suggests that the cytogenetically uninvolved TP53 allele is functional.