TP53 mutations in peripheral mature T and NK cell lymphomas: a whole-exome sequencing study with correlation to p53 expression

• Published in: Human pathology 2018-10, Vol.80, p.145-151
• Main Authors: Huang, Hui-Shan, Liao, Chun-Kai, Liu, Ting-Ting, You, Huey-Ling, Wang, Ming-Chung, Huang, Wan-Ting
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Angioimmunoblastic T-cell lymphoma; Archives & records; Automation; Bioinformatics; Cloning; Deoxyribonucleic acid; Design; DNA; Extranodal nasal-type NK/T-cell lymphoma; Female; Genes; Humans; In Situ Hybridization - methods; Intestinal T-cell lymphoma; Killer Cells, Natural - metabolism; Lymphoma; Lymphoma, Extranodal NK-T-Cell - diagnosis; Lymphoma, Extranodal NK-T-Cell - pathology; Lymphoma, T-Cell, Peripheral - pathology; Male; Middle Aged; Mutation; Mutation - genetics; p53 expression; Peripheral T-cell lymphoma, not otherwise specified; TP53 mutation; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumors; Whole Exome Sequencing - methods
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2018.05.026

Peripheral mature T and NK cell lymphomas consist of a heterogeneous group of neoplasms with cytogenetic and molecular diversities. TP53 mutation is involved in the events of tumorigenesis and present in a variety of cancer subtypes. However, TP53 mutation in peripheral mature T and NK cell lymphomas has not been extensively investigated. In this study, 57 formalin-fixed paraffin-embedded samples were collected for whole-exome sequencing and immunohistochemical study. Ten cases had TP53 mutation variant allele frequency (VAF) of more than 5%, predominantly in intestinal T-cell lymphoma (60%), peripheral T-cell lymphoma, not otherwise specified (22.2%), and extranodal nasal-type NK/T-cell lymphoma (21.7%). Six of 16 (37.5%) cases with 72Pro homozygous genotype showed higher frequency of TP53 mutation VAF > 5% than did those with 72Arg homozygous genotype (P = .044). To a variable extent, overexpression of p53 was observed in 11 of 56 (19.6%) tumors. The percentage of tumor cells with strong p53 staining was positively correlated with TP53 mutation VAF (R2 = 0.95, P < .001). TP53 mutation and p53 expression tended to indicate poor prognosis (P = .054 and P = .009, respectively). In conclusion, we demonstrated TP53 mutation and p53 expression in subtypes of peripheral mature T and NK cell lymphomas and found positive correlation of this immunostaing pattern with the status of TP53 mutation. •A wide range of TP53 mutations across all exons were identified in peripheral mature T and NK cell lymphomas.•The percentage of tumor cells with strong p53 staining was positively correlated with TP53 mutation variant allele frequency.•TP53 mutation and p53 expression tended to indicate poor prognosis.