Shortened Telomeres Involved in a Case With a Jumping Translocation at 1q21

Abstract

The jumping translocation (JT) is a rare chromosomal abnormality in which a specific chromosomal segment translocates onto the ends of various chromosomes (jumps). In most cases, the region distal to 1q21 jumps onto numerous different telomeres. Here we report a molecular study of the JT involving 1q21 found in a patient with acute myelomonocytic leukemia that had transformed from myelodysplastic syndrome (MDS). This is the first report describing the analysis of the molecular structure of the JT. We demonstrated the presence of a stretch of telomeric repeats at the breakpoint by means of a fluorescence in situ hybridization experiment, molecular cloning, and nucleotide sequencing of the fused region. A significant amount of variant telomeric repeats (a telomeric sequence having one-base mismatch within the authentic telomeric repeat TTAGGG) was found in this region. The variant telomeric repeat has been shown to be present in the proximal region of telomeres and does not perform telomeric functions by itself. Therefore, these results indicated that the telomeres had already been critically shortened when the jumps occurred. We suggest that the extended proliferation of cancer cells during the premalignant stage, such as MDS, results in chromosomal instability due to the loss of telomeric functions.

A Newborn with Genital Ambiguity, 45,X/46,XY Mosaicism, a Jumping Chromosome Y, and Congenital Adrenal Hyperplasia

“…It is known, however, that telomeres are very important for maintenance of chromosome stability. Telomeres cap the ends of chromosomes and prevent chromosome fusion [ 7 , 18 , 19 ]. We can only speculate on how the Yp telomere had become attached to the chromosome 8 or 16 telomere.…”

At the Beginning of the End and in the Middle of the Beginning: Structure and Maintenance of Telomeric DNA Repeats and Interstitial Telomeric Sequences

“…ITS sites were implicated in the formation of so-called jumping translocations where a fragment from a donor chromosome is transferred to several recipient chromosomes [ 301 ]. For instance, ITSs were often found at translocation junctions in patients with Prader-Willi syndrome [ 302 , 303 , 304 , 305 , 306 , 307 ], Dandy-Walker malformation [ 308 ] and hematopoietic malignancies including acute myeloid leukemia (AML) [ 309 , 310 , 311 ]. Several reports show involvement of ITSs in constitutional chromosomal abnormalities [ 307 , 312 , 313 , 314 ].…”

Jumping translocations of chromosome 1q occurring by a multi-stage process in an acute myeloid leukemia progressed from myelodysplastic syndrome with a TET2 mutation

“…A literature search revealed 48 cases of myeloid neoplasms with 1q JTs (including our patient, Table 1) [5,6,11,[14][15][16][17][18][19][20][21][22][23][24]. Of 40 patients who did not have AML at the time of diagnosis, 21 (52.5%) transformed to AML and had a poor outcome.…”

“…While several mechanisms have been proposed to explain JT formation, including viral infection, chromosome instability, pericentromeric heterochromatin decondensation, shortened telomeres, and illegitimate recombination between telomere repeat sequences and interstitial telomeric sequences [3,[7][8][9][10][11][12][13], the mechanism of 1q JT formation in patients with myeloid malignancies is still not fully understood. Here, we describe a patient with AML that progressed from a myelodysplastic syndrome (MDS) with pathogenic mutations of the RUNX1, SRSF2, ASXL1, and TET2 genes in association with development of 1q JTs, which supports that the formation of 1q JTs may involve multiple stages and that 1q JTs may represent a very high-risk cytogenetic abnormality with transformation to AML.…”