Distinct Signatures of Chromosomal Involvement in 59 251 Translocations Across 58 Tumor Types. A Novel Perspective

Abstract

Chromosomal translocations are key events in cancer, driving oncogenesis by disrupting and deregulating critical genes. While specific tumor-associated translocations are well studied, the frequencies and distributions of most remain unknown. Additionally, the role of chromosomal reshuffling in translocations has received little attention. This study presents data on the chromosomal involvement in 59 251 translocations reported in 58 tumor entities, including both benign and malignant tumors. Unlike studies focusing on tumor-specific abnormalities identified at the chromosome band level, this study examines translocations at the chromosomal level, offering a novel perspective on their distribution. This broader approach aims to uncover patterns that do not emerge or are disregarded in studies limited to tumor-specific aberrations. The resulting dataset provides a novel resource for deepening our understanding of the chromosomal origins of translocations in neoplasia. Comparisons of translocation frequency distributions among tumor types, when excluding the characteristic tumor-associated translocations, revealed that the patterns of chromosomal involvement in translocations are largely unique to each tumor entity. Statistical analyses of 241 pairwise comparisons of translocation spectra within hematologic disorders, solid tumors, and between groups of hematologic malignancies and both benign and malignant solid tumors showed insignificant/very weak associations (R² ≤ 0.3) in 98% of the comparisons. The findings hence demonstrate that different tumor types are characterized by distinct chromosomal translocation signatures, strongly suggesting that most translocations encountered in tumor cells are not merely random events. Consequently, our study highlights the potential of rare translocations to serve as indicators of disease-specific processes.