Association of Chromosome 17 Aneuploidy, TP53 Deletion, Expression and Its rs1042522 Variant with Multiple Myeloma Risk and Response to Thalidomide/Bortezomib Treatment

SIMPLE SUMMARY: The detailed role of the TP53 p.P72R (rs1042522) variant in the etiology and course of multiple myeloma (MM), as well as its association with chromosome 17 aberrations, has not been analyzed in a such a wide range. In our study, we have explored the significance of the p.P72R variant, expression level of TP53 gene, deletion of TP53 locus and chromosome 17 aneuploidies in MM development, and the response to bortezomib/thalidomide treatment in MM patients. We have shown that the p.R72R variant was associated with a higher age of MM patients at diagnosis and with a higher number of plasma cells. We have found higher expression of TP53 in MM smokers in comparison to MM non-smokers. TP53 gene expression and the p.P72R variant did not affect the MM outcome. ABSTRACT: Multiple myeloma (MM) is a multifactorial genetic disorder caused by interactive effects of environmental and genetic factors. The proper locus of the TP53 gene (17p13.1) and its protein is essential in genomic stability. The most common variant of the TP53 gene—p.P72R (rs1042522)—shows functional variation. The aim of our study was a complex analysis of the TP53 p.P72R variant and TP53 gene expression in relation to chromosomal changes of the TP53 gene locus, as well as MM risk and outcome. Genomic DNA from 129 newly diagnosed MM patients was analyzed by methods of automated DNA sequencing (for TP53 variant analysis) and cIg-FISH (for chromosomal aberrations analysis). RNA was used in real-time PCR to determine the TP53 expression. In MM patients, the TP53 variant was not in Hardy–Weinberg equilibrium. The RR genotype was associated with lower MM risk (OR = 0.44, p = 0.004). A higher number of plasma cells was found in patients with RR genotype in comparison to those with PP + PR genotypes (36.74% vs. 28.30%, p = 0.02). A higher expression of the TP53 gene was observed in PP + PR genotypes vs. RR homozygote (p < 0.001), in smokers vs. non-smokers (p = 0.02). A positive Pearson’s correlation was found between the TP53 expression level and the number of plasma cells (r = 0.26, p = 0.04). The presence of chromosome 17 aberrations with or without TP53 locus did not affect the MM risk and outcome. Similar results were observed in the case of TP53 gene expression and the p.P72R variant.