Association study of a functional copy number variation in the <i>WWOX</i> gene with risk of gliomas among Chinese people

Yu, Ke; Fan, Jin; Ding, Xin; Li, CongYang; Wang, Jun; Xiang, Yang; Wang, Qingsong

doi:10.1002/ijc.28815

Cited by 24 publications

(29 citation statements)

References 24 publications

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“…It was reported that germline variant originally identified as CNV‐67048 of 13.3 Kbp in size mapping to chr16:76929120‐76942453 assembly NCBI36/hg18 (chr16:78337722‐78351055 in GRCh38/hg38) has been linked to the risk of lung cancer, gliomas, ovarian cancer, and also to chronic obstructive pulmonary disease . It must be noted that CNV‐67048 does not correspond to any currently existent nomenclature, however, based on its chromosomal coordinates is the same as esv22307 originally described as a complex variant for both copy number losses but also gains in humans and not just losses as reported in the aforementioned previous studies . It is worth noting that esv22307 lies within the previously described hot spot for germline duplications and deletions within intron 5 of WWOX (Figure ).…”

Section: Wwox Is a Hot Spot For Germline Cnv Polymorphismsmentioning

confidence: 99%

WWOX, the FRA16D gene: A target of and a contributor to genomic instability

Hussain

Liu

Shrock

et al. 2018

Genes Chromosomes & Cancer

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WWOX is one of the largest human genes spanning over 1.11 Mbp in length at chr16q23.1‐q23.2 and containing FRA16D, the second most common chromosomal fragile site. FRA16D is a hot spot of genomic instability, prone to breakage and for causing germline and somatic copy number variations (CNVs). Consequentially WWOX is frequent target for deletions in cancer. Esophageal, stomach, colon, bladder, ovarian, and uterine cancers are those most commonly affected by WWOX deep focal deletions. WWOX deletions significantly correlate with various clinicopathological features in esophageal carcinoma. WWOX is also a common target for translocations in multiple myeloma. By mapping R‐loop (RNA:DNA hybrid) forming sequences (RFLS) we observe this to be a consistent feature aligning with germline and somatic CNV break points at the edges and core of FRA16D spanning from introns 5 to 8 of WWOX. Germline CNV polymorphisms affecting WWOX are extremely common in humans across different ethnic groups. Importantly, structural variants datasets allowed us to identify a specific hot spot for germline duplications and deletions within intron 5 of WWOX coinciding with the 5′ edge of the FRA16D core and various RFLS. Recently, multiple pathogenic CNVs spanning WWOX have been identified associated with neurological conditions such as autism spectrum disorder, infantile epileptic encephalopathies, and other developmental anomalies. Loss of WWOX function has recently been associated with DNA damage repair abnormalities, increased genomic instability, and resistance to chemoradiotherapy. The described observations place WWOX both as a target of and a contributor to genomic instability. Both of these aspects will be discussed in this review.

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Section: Wwox Is a Hot Spot For Germline Cnv Polymorphismsmentioning

confidence: 99%

WWOX, the FRA16D gene: A target of and a contributor to genomic instability

Hussain

Liu

Shrock

et al. 2018

Genes Chromosomes & Cancer

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“…The copy number of a CNV located at 16q23.1-16q23.2 including WWOX is associated with susceptibility to glioma; the decrease in the copy number of the CNV increases a possibility of glioma development [44]. The odds ratio for glioma development is reported 1.21 for 1-copy loss and 1.94 for 2-copy loss.…”

Section: Gliomamentioning

confidence: 99%

CNVs Associated with Susceptibility to Cancers: A Mini-Review

Furuya¹,

Suehiro²,

Namiki³

et al. 2015

JCT

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Copy number variations (CNVs) that are frequent in genome influence on susceptibility of various diseases including cancers. The present mini-review focuses on CNVs associated with susceptibility to the cancers. Since CNVs are different between cancer types, the analysis of the specific CNV makes it possible to estimate the susceptibility to the cancers of interest in individuals. Although it is true that available data on CNVs associated with cancer susceptibility are limited at present, accumulation of the data is accelerated with the research progression of CNVs in near future. Information on CNVs associated with cancer susceptibility is useful for not only cancer research but also personalized healthcare including cancer prevention.

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“…8 Recently, a similar association has been found between the CNV-67048 genetic variant and risk of gliomas. 9 Characteristics of the WWOX protein sequence…”

Section: Introductionmentioning

confidence: 99%

WWOX, the chromosomal fragile site FRA16D spanning gene: Its role in metabolism and contribution to cancer

Richards

Choo

Lee

et al. 2015

Exp Biol Med (Maywood)

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The WWOX gene spans the common chromosomal fragile site FRA16D that is located within a massive (780 kb) intron. The WWOX gene is very long, at 1.1 Mb, which may contribute to the very low abundance of the full-length 1.4 kb mRNA. Alternative splicing also accounts for a variety of aberrant transcripts, most of which are devoid of C-terminal sequences required for WWOX to act as an oxidoreductase. The mouse WWOX gene also spans a chromosomal fragile site implying some sort of functional relationship that confers a selective advantage. The encoded protein domains of WWOX are conserved through evolution (between humans and Drosophila melanogaster) and include WW domains, an NAD -binding site, short-chain dehydrogenase/reductase enzyme and nuclear compartmentalization signals. This homology has enabled functional analyses in D. melanogaster that demonstrate roles for WWOX in reactive oxygen species regulation and metabolism. Indeed the human WWOX gene is also responsive to altered metabolism. Cancer cells typically exhibit altered metabolism (Warburg effect). Many cancers exhibit FRA16D DNA instability that results in aberrant WWOX expression and is associated with poor prognosis for these cancers. It is therefore thought that aberrant WWOX expression contributes to the altered metabolism in cancer. In addition, others have found that a specific (low-expression) allele of WWOX genotype contributes to cancer predisposition.

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Association study of a functional copy number variation in the WWOX gene with risk of gliomas among Chinese people

Cited by 24 publications

References 24 publications

WWOX, the FRA16D gene: A target of and a contributor to genomic instability

WWOX, the FRA16D gene: A target of and a contributor to genomic instability

CNVs Associated with Susceptibility to Cancers: A Mini-Review

WWOX, the chromosomal fragile site FRA16D spanning gene: Its role in metabolism and contribution to cancer

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