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Title: Chromosome 19q13 disruption alters expressions of CYP2A7, MIA and MIA-RAB4B lncRNA and contributes to FAP-like phenotype in APC mutation-negative familial colorectal cancer patients
Authors: Thean L.F.
Wong Y.H.
Lo M.
Loi C.
Chew M.H. 
Tang C.L. 
Cheah P.Y.
Keywords: long untranslated RNA
MIA protein
microRNA 24
PIM2 protein
RAB4B protein
TAOK1 protein
unclassified drug
CYP2A7 protein, human
cytochrome P450 family 2
EGLN2 protein, human
hypoxia inducible factor proline dioxygenase
long untranslated RNA
MIA protein, human
tumor protein
unspecific monooxygenase
3' untranslated region
adenomatous polyposis coli gene
binding site
case report
chromosome 19q
chromosome 19q13
colorectal cancer
controlled study
CYP2A7 gene
familial colon polyposis
gene deletion
gene dosage
gene expression
gene location
gene mutation
gene targeting
genetic association
real time polymerase chain reaction
reverse transcription polymerase chain reaction
young adult
chromosome 19
colon polyposis
colorectal tumor
tumor suppressor gene
Adenomatous Polyposis Coli
Aryl Hydrocarbon Hydroxylases
Chromosomes, Human, Pair 19
Colorectal Neoplasms
Cytochrome P450 Family 2
Extracellular Matrix Proteins
Genes, APC
Hypoxia-Inducible Factor-Proline Dioxygenases
Neoplasm Proteins
RNA, Long Noncoding
Issue Date: 2017
Citation: Thean L.F., Wong Y.H., Lo M., Loi C., Chew M.H., Tang C.L., Cheah P.Y. (2017). Chromosome 19q13 disruption alters expressions of CYP2A7, MIA and MIA-RAB4B lncRNA and contributes to FAP-like phenotype in APC mutation-negative familial colorectal cancer patients. PLoS ONE 12 (3) : e0173772. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: Familial adenomatous polyposis (FAP) is an autosomal-dominantly inherited form of colorectal cancer (CRC) caused by mutation in the adenomatous polyposis coli (APC) gene. Our ability to exhaustively screen for APC mutations identify microsatellite-stable and APCmutation negative familial CRC patients, enabling us to search for novel genes. We performed genome-wide scan on two affected siblings of one family and 88 ethnicity- and gender- matched healthy controls to identify deletions shared by the siblings. Combined loss of heterozygosity, copy number and allelic-specific copy number analysis uncovered 5 shared deletions. Long-range polymerase chain reaction (PCR) confirmed chromosome 19q13 deletion, which was subsequently found in one other family. The 32 kb deleted region harbors the CYP2A7 gene and was enriched with enhancer, repressor and insulator sites. The wildtype allele was lost in the polyps of the proband. Further, real-time RT-PCR assays showed that expressions of MIA and MIA-RAB4B located 35 kb upstream of the deletion, were up-regulated in the polyps compared to the matched mucosa of the proband. MIARAB4B, the read-through long non-coding RNA (lncRNA), RAB4B, PIM2 and TAOK1 share common binding site of a microRNA, miR-24, in their 3'UTRs. PIM2 and TAOK1, two target oncogenes of miR-24, were co-ordinately up-regulated with MIA-RAB4B in the polyps, suggesting that MIA-RAB4B could function as competitive endogenous RNA to titrate miR-24 away from its other targets. The data suggest that the 19.13 deletion disrupted chromatin boundary, leading to altered expression of several genes and lncRNA, could contribute to colorectal cancer via novel genetic and epigenetic mechanisms. © 2017 Thean et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Source Title: PLoS ONE
ISSN: 19326203
DOI: 10.1371/journal.pone.0173772
Rights: Attribution 4.0 International
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