Chromosomal Translocation t(5;12)(p13;q14) Leading to Fusion of High-mobility Group AT-hook 2 Gene With Intergenic Sequences From Chromosome Sub-Band 5p13.2 in Benign Myoid Neoplasms of the Breast: A Second Case

Abstract

Background/Aim: Recently, we reported a myoid hamartoma carrying a t(5;12)(p13;q14) karyotypic aberration leading to fusion of the high-mobility group AT-hook 2 (HMGA2) gene with a sequence from chromosome sub-band 5p13.2. We describe here another benign myoid tumor of the breast with identical genetic aberrations. Materials and Methods: A mammary leiomyomatous tumor found in a 45year-old woman was studied using cytogenetics, fluorescence in situ hybridization, RNA sequencing, reverse transcriptionpolymerase chain reaction and Sanger sequencing. Results: The karyotype of the tumor cells was 46,XX,t(5;12) (p13;q14) [14]. Fluorescence in situ hybridization showed rearrangement of HMGA2, RNA sequencing detected fusion of HMGA2 with a sequence from 5p13.2, whereupon reverse transcription-polymerase chain reaction together with Sanger sequencing verified the HMGA2-fusion transcript. The results were identical to those obtained by us previously in a myoid hamartoma of the breast. Conclusion: The translocation t(5;12)(p13;q14) and fusion of HMGA2 with sequences from sub-band 5p13.2 appear to be recurrent events in benign mammary myoid neoplasms.

Neoplasia-associated Chromosome Translocations Resulting in Gene Truncation

“…Using cytogenetics, fluorescence in situ hybridization, RNA sequencing, reverse transcription-polymerase chain reaction, and Sanger sequencing methodologies, we showed that the tumor cells had an identical genetic profile to that found in the previously examined myoid breast hamartoma. We conclude that a chromosome translocation t(5;12)(p13;q14) resulting in fusion of HMGA2 with a sequence from chromosome subband 5p13.2 is recurrent in benign myoid neoplasms of the breast (124).…”

“…The data indicated that myoid hamartoma is a true neoplasm growing from a mutated mesenchymal stem cell capable of differentiating into smooth muscle cells (123). In 2022, we reported the genetic characterization of a mammary leiomyomatous tumor without signs of malignancy (124). Using cytogenetics, fluorescence in situ hybridization, RNA sequencing, reverse transcription-polymerase chain reaction, and Sanger sequencing methodologies, we showed that the tumor cells had an identical genetic profile to that found in the previously examined myoid breast hamartoma.…”

Fusion of theHMGA2andBNC2Genes in Uterine Leiomyoma With t(9;12)(p22;q14)

“…FISH analysis was performed on metaphase plates using an inhouse prepared HMGA2 break-apart probe as previously described (20)(21)(22). The centromeric (proximal) part of the probe (red signal) was constructed from a pool of clones RP11-185K16, RP11-30I11, and RP11-662G15.…”

“…The centromeric (proximal) part of the probe (red signal) was constructed from a pool of clones RP11-185K16, RP11-30I11, and RP11-662G15. The telomeric (distal) part of the probe (green signal) was constructed from a pool of the clones RP118B13, RP11-745O10, and RP11-263A04 (20)(21)(22).…”

“…The primers are listed in Table I. The methods for cDNA synthesis, in vivo 36: 2654-2661 (2022) RT-PCR amplification, and Sanger sequencing are described elsewhere (22,(24)(25)(26). For the first, outer PCR the primers HMGA2-929F1 and BNC2-9443R1 were used, whereas the primer combinations HMGA2-1012F1 and BNC2-9409R1 were used for the second, inner PCR.…”