Dramatic increase in gene mutational burden after transformation of follicular lymphoma into TdT + B-lymphoblastic leukemia/lymphoma.

Autor:	Belman JP; Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA., Meng W; Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA., Wang HY; Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA., Li J; Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA., Strauser HT; Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA., Rosenfeld AM; Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA., Zhang Q; Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA., Prak ETL; Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA., Wasik M; Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Jazyk:	angličtina
Zdroj:	Cold Spring Harbor molecular case studies [Cold Spring Harb Mol Case Stud] 2020 Feb 03; Vol. 6 (1). Date of Electronic Publication: 2020 Feb 03 (Print Publication: 2020).
DOI:	10.1101/mcs.a004614
Abstrakt:	Transformation of follicular lymphoma (FL) into B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) is rare and results in greatly increased aggressiveness of clinical course. Here we present extensive molecular analysis of this unusual transformation, including immunoglobulin (Ig) gene rearrangement studies, cytogenetic analysis, and whole-exome sequencing (WES) of the patient's FL, B-ALL/LBL, and normal cells. Although FL showed marked somatic hypermutation (SHM) of the Ig genes, SHM appeared to be even more extensive in B-ALL/LBL. Cytogenetically, at least three translocations were identified in the B-ALL/LBL involving the BCL2 , BCL6 , and MYC genes; two of these, the BCL6 and BCL2 gene rearrangements, were already seen at the FL stage. WES identified 751 single-nucleotide variants with high allelic burden in the patient's cells, with the vast majority (575) present exclusively at the B-ALL/LBL stage. Of note, a TAF3 gene mutation was shared by normal, FL, and B-ALL/LBL tissue. A KMT2D nonsense mutation was identified in both FL and B-ALL/LBL and therefore may have contributed directly to lymphomagenesis. Mutations in KDM6A , SMARCA4 , CBX1 , and JMY were specific to the B-ALL/LBL stage, possibly contributing to the B-ALL/LBL transformation. Functionally, these identified mutations may lead to dysregulation of DNA repair, transcription, and cell differentiation. Thus, these genetic changes, together with the identified chromosomal translocations, may have contributed to lymphoma development and progression. Our findings may improve the mechanistic understanding of the FL-B-ALL/LBL transformation and may have therapeutic implications for this aggressive disease. (© 2020 Belman et al.; Published by Cold Spring Harbor Laboratory Press.)
Databáze:	MEDLINE
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