Tumor protein 53 mutations are enriched in diffuse large B-cell lymphoma with irregular CD19 marker expression

Abstract

Accumulating evidence suggests tumor protein 53 (p53) promotes correct cellular differentiation. Thus, mutant TP53 may be more frequent in tumors with irregular differentiation. This study investigated whether TP53 mutations were more frequent in diffuse large B cell lymphoma (DLBCL) that lacked the B cell lineage marker CD19. Sixteen CD19 negative and 78 CD19 positive DLBCL were sequenced for TP53 mutations. Twenty nine tumors had TP53 mutations and were associated with poorer survival. Mutant TP53 was more frequent in CD19 negative lymphomas (81% versus 21%, p < 0.0001). Analysis of other B cell markers revealed a lack of paired box 5 (PAX5) in CD19 positive lymphomas with mutant TP53 (50%), which was more frequent compared to tumors with wild-type TP53 (15%, p = 0.002). In summary, DLBCL lacking CD19 or PAX5 expression were more likely to have mutant TP53, suggesting irregular B cell marker phenotypes are associated with TP53 mutation.Normal functioning of p53 is critical for preventing cancers. We know this because mice with defects in Trp53 are highly tumor prone; in humans inherited TP53 mutations, Li-Fraumeni Syndrome, is characterized by multiple tumor types, and about half of all human cancers contain TP53 mutations (www.iarc. 5,6 . A poorer prognosis is associated with DLBCL with mutant p53 [5][6][7][8][9][10] . Of interest, 10-12% of DLBCL have lost the B cell lineage marker CD19 11,12 and are also associated with a poor prognosis 5,6,12 . Given this, and the data from the PRD mutant mouse, we were interested to determine if mutant p53 might be driving abnormal B cell differentiation that pre-disposes to malignancy. This study investigated the prevalence of TP53 mutations in DLBCL with irregular expression of B cell markers including those that were CD19 negative. ResultsTP53 mutations are enriched in CD19 negative DLBCL. Ninety-four DLBCL were included in the study. The patient demographics and clinical information are provided in Table 1. Sixteen DLBCL were CD19 negative based on a low expression of CD19 positive cells by flow cytometry (a clear visible shift in fluorescence consistent with reduced expression) based on the initial diagnostic assessment. A lack of CD19 positive cells in

Molecular analysis of a CD19-negative diffuse large B-cell lymphoma

“…Regarding DLBCL, some cases have been described as CD19 negative using immunohistochemistry, [9][10][11] but this was not confirmed by flow cytometry, which is more sensitive. 12 To the best of our knowledge, this case is the first report of DLBCL with complete loss of CD19 expression at diagnosis, as demonstrated by flow cytometry, which is the most sensitive technique.…”

Elevation of the TP53 isoform Δ133p53β in glioblastomas: an alternative to mutant p53 in promoting tumor development

“…DNA was extracted from frozen tumors. To detect TP53 mutations, PCR‐amplified exons 4–9 of TP53 were sequenced using previously published primers . Purified PCR products were subjected to Sanger sequencing.…”

Intronic TP53 Polymorphisms Are Associated with Increased Δ133TP53 Transcript, Immune Infiltration and Cancer Risk

“…For all tumour cohorts studied in Dunedin and the Fre lines, PCR was used to amplify the DNA region between exons 4-9 of TP53. The primer sequences used were those published [55]. For amplification of intron 4, the following primers were also used: 5 -AGTTTACCCACTTAATGTGTG-3 ; 5 -CAGGAGATGGAGGCTGCAGTG-3 ; 5 -CAAGGCAGGCAGATCACCTG-3 (sense primers) and 5 -CTATAGGTGTGCACCACCATG-3 ; 5 -CCTCCTGCAACCCACTAG-3 ; 5 -CCACAGCTGCACAGGGCAGG-3 (antisense primers).…”