Targeted Sequencing in Chromosome 17q Linkage Region Identifies Familial Glioma Candidates in the Gliogene Consortium

Abstract

Glioma is a rare, but highly fatal, cancer that accounts for the majority of malignant primary brain tumors. Inherited predisposition to glioma has been consistently observed within non-syndromic families. Our previous studies, which involved non-parametric and parametric linkage analyses, both yielded significant linkage peaks on chromosome 17q. Here, we use data from next generation and Sanger sequencing to identify familial glioma candidate genes and variants on chromosome 17q for further investigation. We applied a filtering schema to narrow the original list of 4830 annotated variants down to 21 very rare (<0.1% frequency), non-synonymous variants. Our findings implicate the MYO19 and KIF18B genes and rare variants in SPAG9 and RUNDC1 as candidates worthy of further investigation. Burden testing and functional studies are planned.

How myosin organization of the actin cytoskeleton contributes to the cancer phenotype

“…In our experiments, we did not find any changes in expression of MYO19 in prostate cancer cell lines [5]. However, a recent report of a linkage analysis for part of chromosome 17 identified MYO19 as a possible candidate for Glioma, with 2 missense mutations identified [105]. However, the chromosome positions reported currently appear to map to an upstream lincRNA and not to the MYO19 gene.…”

Myo19 is an outer mitochondrial membrane motor and effector of starvation-induced filopodia

“…Myo19 has recently been implicated in gliomagenesis (Jalali et al, 2015). Moreover, mitochondria were found in filopodia of glioblastoma cells that actively penetrate extracellular matrix (Arismendi-Morillo et al, 2012).…”

KIF18B promotes the proliferation of pancreatic ductal adenocarcinoma via activating the expression of CDCA8

“…Additionally, KIF18B is involved in the separation of chromosomes in mitosis and organizing astral MTs (Kim, Fonseca, & Stumpff, 2014). In recent years, studies have demonstrated that KIF18B was involved in the growth and development of multiple cancers (Jalali et al, 2015;Wu et al, 2018). KIF18B is highly expressed in cervical cancer tissue and further promotes the proliferation and migration of cervical cancer cells (Wu et al, 2018).…”