Prognostic significance of isochromosome 17q in hematologic malignancies

Abstract

Isochromosome 17q [i(17q)] with its two identical long arms is formed by duplication of the q arm and loss of the short p arm. The breakpoint in chromosome 17 that allows the formation of this isochromosome is located at 17p11.2, and the ~240 kb region with its large, palindromic, low-copy repeat sequences are present here. The region is highly unstable and susceptible to a variety of genomic alterations which may be induced by or without toxic agents. One molecular consequence of i(17q) development is the obligatory loss of a single TP53 allele of the tumor suppressor P53 protein located at 17p13.1. Isochromosome 17q is involved in cancer development and progression. It occurs in combination with other chromosomal defects (complex cytogenetics), and rarely as a single mutation. The i(17q) rearrangement has been described as the most common chromosomal aberration in primitive neuroectodermal tumors and medulloblastomas. This isochromosome is also detected in different hematological disorders. In this article, we analyze literature data on the presence of i(17q) in proliferative disorders of the hematopoietic system in the context of its role as a prognostic factor of disease progression. The case reports are added to support the presented data. Currently, there are no indications for the use of specific treatment regimens in the subjects with a presence of the isochromosome 17q. Thus, it is of importance to continue studies on the prognostic role of this abnormality and even single cases should be reported as they may be used for further statistical analyses or meta-analyses.

Acute promyelocytic leukemia with torque teno mini virus (TTMV)::RARAfusion: an approach to screening and diagnosis

“…26 APL infrequently demonstrates iso(17q) or idic(17p11), where it usually co-occurs with t(15;17) resulting in an additional copy of PML::RARA but can also be an isolated finding associated with a cryptic PML::RARA. [27][28][29] Interestingly, two of the described cases of APL with TTMV::RARA fusion demonstrate iso(17q) or idic(17p), suggesting that this may represent a characteristic chromosomal abnormality. Indeed, several cases of AML with promyelocytic features, iso(17q), and no detectable PML::RARA have been described, possibly representing APL with unidentified TTMV::RARA fusions.…”

“…A final objective was to assemble and characterize a TTMV::RARA contig or contigs. To this end, various assemblers including TRINITY 21 (version 2.5.1) for RNA data and VELVET 22 (version 1.2.10 using k-mer lengths of [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] for DNA data were applied to paired-end reads with a blastn alignment of either read of the pair to TTMV, supplemented by paired-end reads where at least one read of the pair had a partial local alignment to the approximate RARA breakpoint cluster region but without a supplementary, secondary, or primary alignment resolving the 5' or 3' part of the read. The resulting contigs were then aligned to TTMV by blastn and locally aligned to the human genome by bwa mem or blat in order to maximally characterize the fusion event.…”

Background, Diagnosis, Types, Management/Prevention and Implications of Chromosomal Abnormalities

“…Isochromes are created as a result of incorrect division, specifically U type strand division, which results in dicentric or bi centromeric chromosomes. Pallister-Killian syndrome, caused by isochromosome 12 p, and cat eye syndrome, produced by fusion of the short arm of chromosome 22 and on isochromosome 17q, are two syndromes related with isochromosomes [17].…”

Hybrid or Mixed Myelodysplastic/Myeloproliferative Disorders – Epidemiological Features and Overview

“…In this case, it often presents as MDS/MPN overlap syndrome. The median age is around 60 years, with the typical male predominance (23)(24)(25)(26)(27)(28)(29)(30). Patients often present with anemia, leukocytosis, and splenomegaly.…”

“…Refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T) was initially proposed as a provisional entity in the WHO 2001 classification of myeloid neoplasms (20) and only 2016 recognized as a formal subgroup (MDS/MPN-RS-T) of MDS/MPN by the latest version of the WHO-classification (1). Additional entities that have been discussed and might represent separate entities of MDS/MPN in future classifications are MDS with isolated del(5q) and JAK2-V617F mutation and MDS/MPN with isolated isochromosome 17q (21)(22)(23)(24)(25)(26)(27)(28)(29)(30).…”