Association of Chromosome 17 Aneuploidy, <i>TP53</i> Deletion, Expression and Its rs1042522 Variant with Multiple Myeloma Risk and Response to Thalidomide/Bortezomib Treatment
Multiple myeloma (MM) is a multifactorial genetic disorder caused by interactive effects of environmental and genetic factors. The proper <i>locus</i> of the <i>TP53</i> gene (17p13.1) and its protein is essential in genomic stability. The most common variant of the <i>...
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MDPI AG
2023-09-01
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| author | Sylwia Popek-Marciniec Wojciech Styk Magdalena Wojcierowska-Litwin Sylwia Chocholska Aneta Szudy-Szczyrek Marzena Samardakiewicz Grazyna Swiderska-Kolacz Joanna Czerwik-Marcinkowska Szymon Zmorzynski |
| author_facet | Sylwia Popek-Marciniec Wojciech Styk Magdalena Wojcierowska-Litwin Sylwia Chocholska Aneta Szudy-Szczyrek Marzena Samardakiewicz Grazyna Swiderska-Kolacz Joanna Czerwik-Marcinkowska Szymon Zmorzynski |
| author_sort | Sylwia Popek-Marciniec |
| collection | DOAJ |
| description | Multiple myeloma (MM) is a multifactorial genetic disorder caused by interactive effects of environmental and genetic factors. The proper <i>locus</i> of the <i>TP53</i> gene (17p13.1) and its protein is essential in genomic stability. The most common variant of the <i>TP53</i> gene—p.P72R (rs1042522)—shows functional variation. The aim of our study was a complex analysis of the <i>TP53</i> p.P72R variant and <i>TP53</i> gene expression in relation to chromosomal changes of the <i>TP53</i> gene <i>locus</i>, as well as MM risk and outcome. Genomic DNA from 129 newly diagnosed MM patients was analyzed by methods of automated DNA sequencing (for <i>TP53</i> variant analysis) and cIg-FISH (for chromosomal aberrations analysis). RNA was used in real-time PCR to determine the <i>TP53</i> expression. In MM patients, the <i>TP53</i> variant was not in Hardy–Weinberg equilibrium. The RR genotype was associated with lower MM risk (OR = 0.44, <i>p</i> = 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%, <i>p</i> = 0.02). A higher expression of the <i>TP53</i> gene was observed in PP + PR genotypes vs. RR homozygote (<i>p</i> < 0.001), in smokers vs. non-smokers (<i>p</i> = 0.02). A positive Pearson’s correlation was found between the <i>TP53</i> expression level and the number of plasma cells (r = 0.26, <i>p</i> = 0.04). The presence of chromosome 17 aberrations with or without <i>TP53 locus</i> did not affect the MM risk and outcome. Similar results were observed in the case of <i>TP53</i> gene expression and the p.P72R variant. |
| first_indexed | 2024-03-10T21:47:25Z |
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| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T21:47:25Z |
| publishDate | 2023-09-01 |
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| series | Cancers |
| spelling | doaj.art-3aa460ae726e47b89f86dfb1227c36ac2023-11-19T14:09:59ZengMDPI AGCancers2072-66942023-09-011519474710.3390/cancers15194747Association of Chromosome 17 Aneuploidy, <i>TP53</i> Deletion, Expression and Its rs1042522 Variant with Multiple Myeloma Risk and Response to Thalidomide/Bortezomib TreatmentSylwia Popek-Marciniec0Wojciech Styk1Magdalena Wojcierowska-Litwin2Sylwia Chocholska3Aneta Szudy-Szczyrek4Marzena Samardakiewicz5Grazyna Swiderska-Kolacz6Joanna Czerwik-Marcinkowska7Szymon Zmorzynski8Laboratory of Genetics, Academy of Zamosc, 22-400 Zamosc, PolandDepartment of Psychology, Medical University of Lublin, 20-059 Lublin, PolandDepartment of Cancer Genetics with Cytogenetic Laboratory, Medical University of Lublin, 20-059 Lublin, PolandChair and Department of Hematooncology and Bone Marrow Transplantation, Medical University of Lublin, 20-059 Lublin, PolandChair and Department of Hematooncology and Bone Marrow Transplantation, Medical University of Lublin, 20-059 Lublin, PolandDepartment of Psychology, Medical University of Lublin, 20-059 Lublin, PolandInstitute of Biology, Jan Kochanowski University, 25-369 Kielce, PolandInstitute of Biology, Jan Kochanowski University, 25-369 Kielce, PolandLaboratory of Genetics, Academy of Zamosc, 22-400 Zamosc, PolandMultiple myeloma (MM) is a multifactorial genetic disorder caused by interactive effects of environmental and genetic factors. The proper <i>locus</i> of the <i>TP53</i> gene (17p13.1) and its protein is essential in genomic stability. The most common variant of the <i>TP53</i> gene—p.P72R (rs1042522)—shows functional variation. The aim of our study was a complex analysis of the <i>TP53</i> p.P72R variant and <i>TP53</i> gene expression in relation to chromosomal changes of the <i>TP53</i> gene <i>locus</i>, as well as MM risk and outcome. Genomic DNA from 129 newly diagnosed MM patients was analyzed by methods of automated DNA sequencing (for <i>TP53</i> variant analysis) and cIg-FISH (for chromosomal aberrations analysis). RNA was used in real-time PCR to determine the <i>TP53</i> expression. In MM patients, the <i>TP53</i> variant was not in Hardy–Weinberg equilibrium. The RR genotype was associated with lower MM risk (OR = 0.44, <i>p</i> = 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%, <i>p</i> = 0.02). A higher expression of the <i>TP53</i> gene was observed in PP + PR genotypes vs. RR homozygote (<i>p</i> < 0.001), in smokers vs. non-smokers (<i>p</i> = 0.02). A positive Pearson’s correlation was found between the <i>TP53</i> expression level and the number of plasma cells (r = 0.26, <i>p</i> = 0.04). The presence of chromosome 17 aberrations with or without <i>TP53 locus</i> did not affect the MM risk and outcome. Similar results were observed in the case of <i>TP53</i> gene expression and the p.P72R variant.https://www.mdpi.com/2072-6694/15/19/4747<i>TP53</i> variantp.P72R polymorphism<i>TP53</i> expression17p13 <i>locus</i>plasma cell myelomaplasma cells |
| spellingShingle | Sylwia Popek-Marciniec Wojciech Styk Magdalena Wojcierowska-Litwin Sylwia Chocholska Aneta Szudy-Szczyrek Marzena Samardakiewicz Grazyna Swiderska-Kolacz Joanna Czerwik-Marcinkowska Szymon Zmorzynski Association of Chromosome 17 Aneuploidy, <i>TP53</i> Deletion, Expression and Its rs1042522 Variant with Multiple Myeloma Risk and Response to Thalidomide/Bortezomib Treatment Cancers <i>TP53</i> variant p.P72R polymorphism <i>TP53</i> expression 17p13 <i>locus</i> plasma cell myeloma plasma cells |
| title | Association of Chromosome 17 Aneuploidy, <i>TP53</i> Deletion, Expression and Its rs1042522 Variant with Multiple Myeloma Risk and Response to Thalidomide/Bortezomib Treatment |
| title_full | Association of Chromosome 17 Aneuploidy, <i>TP53</i> Deletion, Expression and Its rs1042522 Variant with Multiple Myeloma Risk and Response to Thalidomide/Bortezomib Treatment |
| title_fullStr | Association of Chromosome 17 Aneuploidy, <i>TP53</i> Deletion, Expression and Its rs1042522 Variant with Multiple Myeloma Risk and Response to Thalidomide/Bortezomib Treatment |
| title_full_unstemmed | Association of Chromosome 17 Aneuploidy, <i>TP53</i> Deletion, Expression and Its rs1042522 Variant with Multiple Myeloma Risk and Response to Thalidomide/Bortezomib Treatment |
| title_short | Association of Chromosome 17 Aneuploidy, <i>TP53</i> Deletion, Expression and Its rs1042522 Variant with Multiple Myeloma Risk and Response to Thalidomide/Bortezomib Treatment |
| title_sort | association of chromosome 17 aneuploidy i tp53 i deletion expression and its rs1042522 variant with multiple myeloma risk and response to thalidomide bortezomib treatment |
| topic | <i>TP53</i> variant p.P72R polymorphism <i>TP53</i> expression 17p13 <i>locus</i> plasma cell myeloma plasma cells |
| url | https://www.mdpi.com/2072-6694/15/19/4747 |
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