Identification of polymorphisms in ultraconserved elements associated with clinical outcomes in locally advanced colorectal adenocarcinoma

Lin, Moubin; Eng, Cathy; Hawk, Ernest T.; Huang, Maosheng; Lin, Jie; Gu, Jian; Ellis, Lee M.; Wu, Xifeng

doi:10.1002/cncr.27653

Cited by 16 publications

(14 citation statements)

References 32 publications

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“…Bao et al (2016) for example found association between rs8004379 and prostate cancer-specific mortality. SNPs within UCEs may also be valuable prognostic biomarkers for patients with locally advanced colorectal cancer who receive 5-fluorouracil-based chemotherapy (Lin et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Genetic Variations of Ultraconserved Elements in the Human Genome

Habic

Mattick

Calin

et al. 2019

OMICS: A Journal of Integrative Biology

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Ultraconserved elements (UCEs) are among the most popular DNA markers for phylogenomic analysis. In at least three of five placental mammalian genomes (human, dog, cow, mouse, and rat), 2189 UCEs of at least 200 bp in length that are identical have been identified. Most of these regions have not yet been functionally annotated, and their associations with diseases remain largely unknown. This is an important knowledge gap in human genomics with regard to UCE roles in physiologically critical functions, and by extension, their relevance for shared susceptibilities to common complex diseases across several mammalian organisms in the event of their polymorphic variations. In the present study, we remapped the genomic locations of these UCEs to the latest human genome assembly, and examined them for documented polymorphisms in sequenced human genomes. We identified 29,983 polymorphisms within analyzed UCEs, but revealed that a vast majority exhibits very low minor allele frequencies. Notably, only 112 of the identified polymorphisms are associated with a phenotype in the Ensembl genome browser. Through literature analyses, we confirmed associations of 37 (i.e., out of the 112) polymorphisms within 23 UCEs with 25 diseases and phenotypic traits, including, muscular dystrophies, eye diseases, and cancers (e.g., familial adenomatous polyposis). Most reports of UCE polymorphism-disease associations appeared to be not cognizant that their candidate polymorphisms were actually within UCEs. The present study offers strategic directions and knowledge gaps for future computational and experimental work so as to better understand the thus far intriguing and puzzling role(s) of UCEs in mammalian genomes.

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Section: Discussionmentioning

confidence: 99%

Genetic Variations of Ultraconserved Elements in the Human Genome

Habic

Mattick

Calin

et al. 2019

OMICS: A Journal of Integrative Biology

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“…Different genes and SNPs have been correlated with clinical stage, presence of lymph node metastasis, clinical outcome, increased survival, follow-up after treatment and the risk of recurrence in CRC patients. These markers may be used as a supplement to the tumour lymph nodes metastasis (TNM) staging system, which alone cannot predict cancer prognosis [ 34 – 36 ].…”

Section: Discussionmentioning

confidence: 99%

CD93 gene polymorphism is associated with disseminated colorectal cancer

Olsen

Lindh

Vorkapić

et al. 2015

Int J Colorectal Dis

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PurposeCluster of differentiation 93 (CD93) is involved in apoptosis and inflammation and has a suggested role in angiogenesis, and all of which are involved in the development and dissemination of cancer. We evaluated the expression of CD93 and the association with two single nucleotide polymorphisms (SNPs), rs2749812 and rs2749817, as possible biomarkers in colorectal cancer (CRC).MethodsTissue levels and plasma levels of CD93 were measured using an enzyme-linked immunosorbent assay (ELISA). Expression of CD93 was determined by immunohistochemistry, western blot and gene expression analysis. Genotype frequencies were established for the SNPs by real-time polymerase chain reaction (PCR), and the association with tumour stage and survival was analysed.ResultsTotal CD93 levels were 82 % higher (P < 0.001) in tumours compared to matched normal tissues. Mean levels of soluble CD93 in plasma were 30 % lower (P < 0.001) in the patients compared to the controls. The T/T genotype of SNP rs2749817 was more common in stage IV patients, with consequently higher risk of CRC death (T/T vs. C/C and C/T; hazard ratio (HR) = 1.73, 95 % confidence interval (CI) = 1.11–2.67, P = 0.014), and was associated with a higher risk of CRC recurrence after radical operation (T/T vs. C/C and C/T; HR = 2.07, CI = 1.22–3.51, P = 0.007).ConclusionsWe showed that the T/T genotype of SNP rs2749817 is associated with disseminated cancer at diagnosis and an increased recurrence rate after radical operation. Patients with this genotype may benefit from early identification.

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“…Additionally, rs10211390 in uc.54 was associated with more advanced CRC stages degrees for patients who had an increased recurrence risk after fluoropyrimidine‐based chemotherapy (5FU). This variation was highlighted as a promising prognostic marker (M. Lin, Eng, Hawk, Huang, Lin, et al, ).…”

Section: Single Nucleotide Variation In T‐ucrsmentioning

confidence: 99%

Highlighting transcribed ultraconserved regions in human diseases

et al. 2019

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Ultraconserved regions (UCRs) are 481 DNA segments longer than 200 bp in length that are completely conserved among human, mouse, and rat and, extremely conserved across disparate taxa. More than 90% of UCRs are transcribed (T‐UCRs) in normal tissues, but most of them remain uncharacterized. In addition, it was demonstrated that T‐UCRs have a tissue‐specific expression, and a differential expression profile between tumors and other diseases, which suggests that most of T‐UCRs may have an important role in cell processes. However, there is little information about T‐UCR characterization or about their molecular mechanisms of action. Taking this into account, in this study, we aim to summarize deregulated T‐UCRs in human diseases, emphasizing the ones with stronger functional evidences that are associated with important cell pathways and have a detailed molecular characterization. This article is characterized under: RNA in Disease and Development > RNA in Disease Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs

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Identification of polymorphisms in ultraconserved elements associated with clinical outcomes in locally advanced colorectal adenocarcinoma

Cited by 16 publications

References 32 publications

Genetic Variations of Ultraconserved Elements in the Human Genome

Genetic Variations of Ultraconserved Elements in the Human Genome

CD93 gene polymorphism is associated with disseminated colorectal cancer

Highlighting transcribed ultraconserved regions in human diseases

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