Exploring the frequency of a TP53 polyadenylation signal variant in tumor DNA from patients diagnosed with lung adenocarcinomas, sarcomas and uterine leiomyomas

• Published in: Genetics and molecular biology Vol. 46; no. 3 Suppl 1; p. e20230133
• Main Authors: Vieira, Igor Araujo, Viola, Guilherme Danielski, Pezzi, Eduarda Heidrich, Kowalski, Thayne Woycinck, Fernandes, Bruna Vieira, Andreis, Tiago Finger, Bom, Natascha, Sonnenstrahl, Giulianna, Rocha, Yasminne Marinho de Araújo, Corrêa, Bruno da Silveira, Donatti, Luiza Mezzomo, Sant'Anna, Gabriela Dos Santos, Corleta, Helena von Eye, Brum, Ilma Simoni, Rosset, Clévia, Vianna, Fernanda Sales Luiz, Macedo, Gabriel S, Palmero, Edenir Inez, Ashton-Prolla, Patricia
• Format: Journal Article
• Language: English; Portuguese
• Published: Brazil Sociedade Brasileira de Genética 01.01.2023
• Subjects: 3’ untranslated region; BIOCHEMISTRY & MOLECULAR BIOLOGY; GENETICS & HEREDITY; non-coding variant; rs78378222; somatic analyses; TP53 gene; 3’ untranslated region; rs78378222; non-coding variant; TP53 gene; somatic analyses
• ISSN: 1415-4757; 1678-4685; 1678-4685
• DOI: 10.1590/1678-4685-GMB-2023-0133

The TP53 3'UTR variant rs78378222 A>C has been detected in different tumor types as a somatic alteration that reduces p53 expression through modification of polyadenylation and miRNA regulation. Its prevalence is not yet known in all tumors. Herein, we examine tumor tissue prevalence of rs7837822 in Brazilian cohorts of patients from south and southeast regions diagnosed with lung adenocarcinoma (LUAD, n=586), sarcoma (SARC, n=188) and uterine leiomyoma (ULM, n=41). The minor allele (C) was identified in heterozygosity in 6/586 LUAD tumors (prevalence = 1.02 %) and none of the SARC and ULM samples. Additionally, next generation sequencing analysis revealed that all variant-positive tumors (n=4) with sample availability had additional pathogenic or likely pathogenic somatic variants in the TP53 coding regions. Among them, 3/4 (75 %) had the same pathogenic or likely pathogenic sequence variant (allele frequency <0.05 in tumor DNA) namely c.751A>C (p.Ile251Leu). Our results indicate a low somatic prevalence of rs78378222 in LUAD, ULM and SARC tumors from Brazilian patients, which suggests that no further analysis of this variant in the specific studied regions of Brazil is warranted. However, these findings should not exclude tumor molecular testing of this TP53 3'UTR functional variant for different populations.