Novel Susceptibility Genes Drive Familial Non-Medullary Thyroid Cancer in a Large Consanguineous Kindred

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 May 13

PMID 37175943

Authors

Pierre Majdalani

Uri Yoel

Tayseer Nasasra

Merav Fraenkel

Alon Haim

Neta Loewenthal

Raz Zarivach

Eli Hershkovitz

Ruti Parvari

Affiliations

Soon will be listed here.

Abstract

Familial non-medullary thyroid cancer (FNMTC) is a well-differentiated thyroid cancer (DTC) of follicular cell origin in two or more first-degree relatives. Patients typically demonstrate an autosomal dominant inheritance pattern with incomplete penetrance. While known genes and chromosomal loci account for some FNMTC, the molecular basis for most FNMTC remains elusive. To identify the variation(s) causing FNMTC in an extended consanguineous family consisting of 16 papillary thyroid carcinoma (PTC) cases, we performed whole exome sequence (WES) analysis of six family patients. We demonstrated an association of , , and genes with FNMTC. The variations in these genes may affect the structures of their encoded proteins and, thus, their function. The most promising causative gene is which has high expression in the thyroid, and its protein-protein interactions (PPIs) suggest predisposition of PTC through ARHGEF28-SQSTM1-TP53 or ARHGEF28-PTCSC2-FOXE1-TP53 associations. Using DNA from a patient's thyroid malignant tissue, we analyzed the possible cooperation of somatic variations with these genes. We revealed two somatic heterozygote variations in and genes known to implicate thyroid cancer. Thus, the predisposition by the germline variations and a second hit by somatic variations could lead to the progression to PTC.

Citing Articles

Chromosomal localization of mutated genes in non-syndromic familial thyroid cancer.

Jiang Y, Xia Y, Han Z, Hu Y, Huang T Front Oncol. 2024; 14:1286426.

PMID: 38571492 PMC: 10987779. DOI: 10.3389/fonc.2024.1286426.

FOXE1 Gene is a Probable Tumor Suppressor Gene with Decreased Expression as Papillary Thyroid Cancers Grow, and is Absent in Anaplastic Thyroid Cancers.

Hajian R, Javadirad S, Kolahdouzan M Biochem Genet. 2024; 62(6):4317-4334.

PMID: 38296906 DOI: 10.1007/s10528-023-10642-z.

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