CDKN2A
变色
套细胞淋巴瘤
染色体不稳定性
基因组不稳定性
生物
癌症研究
遗传学
比较基因组杂交
胚泡
单亲二体
淋巴瘤
染色体
癌症
基因
核型
DNA
免疫学
DNA损伤
作者
Lukas D. Streich,Madina Sukhanova,Xinyan Lu,Yihua Chen,Girish Venkataraman,Stephanie Mathews,Shanxiang Zhang,Katalin Kelemen,Jeremy Segal,Juehua Gao,Leo I. Gordon,Qing Chen,Amir Behdad
摘要
Abstract Aggressive morphologic variants of mantle cell lymphoma (MCL), including blastoid and pleomorphic (B/P‐MCL), are rare and associated with poor clinical outcomes. The genomic landscape of these variants remains incompletely explored. In this multi‐institutional study, we describe recurrent mutations and novel genomic copy number alterations (CNAs) in B/P‐MCL, using next generation sequencing and SNP‐array. Chromothripsis, a recently described phenomenon of massive chromosomal rearrangements, was identified in eight of 13 (62%) B/P MCL cases, and a high degree of genomic complexity with frequent copy number gains and losses was also seen. In contrast, a comparative cohort of nine cases of conventional MCL (C‐MCL) showed no chromothripsis and less complexity. Twelve of 13 (92%) B/P‐MCL cases showed loss of CDKN2A / B (6 biallelic and 6 monoallelic losses); while only one C‐MCL showed monoallelic CDKN2A / B loss. In B/P‐MCL, TP53 was the most commonly mutated gene, with mutations present in eight cases (62%), six of which showed concurrent loss of chromosome 17p. Of the eight cases with chromothripsis, six (85%) harbored TP53 mutations. Other recurrent mutations in B/P‐MCL included ATM (7, 53%), CCND1 (5, 38%), NOTCH1 (2, 18%), NOTCH2 , and BIRC3 (each in 3, 23%). Here, we describe high genomic instability associated with chromothripsis and a high frequency of CDKN2A/B and TP53 alterations in the aggressive variants of MCL. The nonrandom chromothripsis events observed in B/P‐MCL may be an indicator of clinically aggressive MCL. In addition, frequent CDKN2A deletion and high genomic instability may provide potential targets for alternative treatment.
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