TY - JOUR

T1 - The rs78378222 prevalence and the copy loss of the protective allele A in the tumor tissue of diffuse large B-cell lymphoma

AU - Voropaeva, Elena N.

AU - Orlov, Yuriy L.

AU - Pospelova, Tatiana I.

AU - Gurageva, Anna A.

AU - Voevoda, Mikhail I.

AU - Maksimov, Vladimir N.

AU - Seregina, Olga B.

AU - Churkina, Maria I.

N1 - © 2020 Voropaeva et al.

PY - 2020/11/12

Y1 - 2020/11/12

N2 - Background: Rare single nucleotide polymorphisms (SNPs) are likely to be a crucial genetic factor for human diseases, including cancer. rs78378222 is rare SNP in 3′-untranslated region (UTR) of TP53 gene leading to disturbance of 3′-end mRNA processing. The frequency of rs78378222 varies in several studied populations. The meta-analysis of 34 genome-wide association studies indicated that rs78378222 was significantly associated with an increased risk of cancer overall. Bioinformatic analysis indicates that somatic loss of the protective A allele of rs78378222 occurs in the tumor tissue of some malignant. The goal of the current study is to document the rs78378222 prevalence and evaluate the copy loss status of the protective allele A in the tumor tissue of patients with diffuse large B-cell lymphoma (DLBCL). Methods: Total DNA was isolated from FFPE-samples and peripheral blood of patients with DLBCL and comparable in age and sex controls. rs78378222 genotyping was performed by the PCR-RFLP method using restriction endonuclease HindIII. Direct Sanger’s sequencing was used to confirm the presence of C allele of the rs78378222. The search for TP53 gene mutations was carried out by Sanger’s direct sequencing method, according to the IARC protocol. Results: The result of genotyping of 136 DNA samples from DLBCL tumor tissue suggested that frequency of the rs78378222 was 11/136 (8.1%). Rare allele C frequency was 11/272 (4.2%). A total of 5/11 DLBCL rs78378222 heterozygous samples had the heterozygosity loss in the TP53 gene. Only one of these cases was combined with TP53 gene mutations which have proven oncogenic potential—p. Arg196Gln, other four cases have not mutations in the coding regions of gene. Conclusions: At the stages of DLBCL initiation or progression a loss of the protective allele A of rs78378222 occurs. Further efforts are needed to study possible molecular mechanisms underlying somatic alterations in DLBCL in this region of the TP53 3′-UTR as well as functional studies to illustrate how the presents of rs78378222 may affect tumor progression of lymphoma.

AB - Background: Rare single nucleotide polymorphisms (SNPs) are likely to be a crucial genetic factor for human diseases, including cancer. rs78378222 is rare SNP in 3′-untranslated region (UTR) of TP53 gene leading to disturbance of 3′-end mRNA processing. The frequency of rs78378222 varies in several studied populations. The meta-analysis of 34 genome-wide association studies indicated that rs78378222 was significantly associated with an increased risk of cancer overall. Bioinformatic analysis indicates that somatic loss of the protective A allele of rs78378222 occurs in the tumor tissue of some malignant. The goal of the current study is to document the rs78378222 prevalence and evaluate the copy loss status of the protective allele A in the tumor tissue of patients with diffuse large B-cell lymphoma (DLBCL). Methods: Total DNA was isolated from FFPE-samples and peripheral blood of patients with DLBCL and comparable in age and sex controls. rs78378222 genotyping was performed by the PCR-RFLP method using restriction endonuclease HindIII. Direct Sanger’s sequencing was used to confirm the presence of C allele of the rs78378222. The search for TP53 gene mutations was carried out by Sanger’s direct sequencing method, according to the IARC protocol. Results: The result of genotyping of 136 DNA samples from DLBCL tumor tissue suggested that frequency of the rs78378222 was 11/136 (8.1%). Rare allele C frequency was 11/272 (4.2%). A total of 5/11 DLBCL rs78378222 heterozygous samples had the heterozygosity loss in the TP53 gene. Only one of these cases was combined with TP53 gene mutations which have proven oncogenic potential—p. Arg196Gln, other four cases have not mutations in the coding regions of gene. Conclusions: At the stages of DLBCL initiation or progression a loss of the protective allele A of rs78378222 occurs. Further efforts are needed to study possible molecular mechanisms underlying somatic alterations in DLBCL in this region of the TP53 3′-UTR as well as functional studies to illustrate how the presents of rs78378222 may affect tumor progression of lymphoma.

KW - Cancer

KW - Diffuse large B-cell lymphoma

KW - Genotyping

KW - Medical genetics

KW - Nucleotide polymorphism

KW - Protective allele

KW - Rs78378222

KW - TP53 gene

KW - CANCERS

KW - POLYADENYLATION SIGNAL

KW - GLIOMA

KW - RISK

KW - GERMLINE VARIANT

KW - PREDISPOSITION

KW - RS1625895

KW - rs78378222

KW - MUTATIONS

KW - TP53

KW - VARIANT RS78378222

UR - http://www.scopus.com/inward/record.url?scp=85095868516&partnerID=8YFLogxK

U2 - 10.7717/peerj.10335

DO - 10.7717/peerj.10335

M3 - Article

C2 - 33240649

AN - SCOPUS:85095868516

VL - 8

JO - PeerJ

JF - PeerJ

SN - 2167-8359

M1 - e10335

ER -