Relative telomere lengths in tumor and normal mucosa are related to disease progression and chromosome instability profiles in colorectal cancer

Suraweera, Nirosha, Mouradov, Dmitri, Li, Shan, Jorissen, Robert N., Hampson, Debbie, Ghosh, Anil, Sengupta, Neel, Thaha, Mohamed, Ahmed, Shafi, Kirwan, Michael, Aleva, Floor, Propper, David, Feakins, Roger M., Vulliamy, Tom, Elwood, Ngaire J., Tian, Pei, Ward, Robyn L., Hawkins, Nicholas J., Xu, Zheng-Zhou, Molloy, Peter L., Jones, Ian T., Croxford, Matthew, Gibbs, Peter, Silver, Andrew and Sieber, Oliver M. (2016) Relative telomere lengths in tumor and normal mucosa are related to disease progression and chromosome instability profiles in colorectal cancer. Oncotarget, 7 24: 36474-36488. doi:10.18632/oncotarget.9015


Author Suraweera, Nirosha
Mouradov, Dmitri
Li, Shan
Jorissen, Robert N.
Hampson, Debbie
Ghosh, Anil
Sengupta, Neel
Thaha, Mohamed
Ahmed, Shafi
Kirwan, Michael
Aleva, Floor
Propper, David
Feakins, Roger M.
Vulliamy, Tom
Elwood, Ngaire J.
Tian, Pei
Ward, Robyn L.
Hawkins, Nicholas J.
Xu, Zheng-Zhou
Molloy, Peter L.
Jones, Ian T.
Croxford, Matthew
Gibbs, Peter
Silver, Andrew
Sieber, Oliver M.
Title Relative telomere lengths in tumor and normal mucosa are related to disease progression and chromosome instability profiles in colorectal cancer
Journal name Oncotarget   Check publisher's open access policy
ISSN 1949-2553
Publication date 2016-04-26
Year available 2016
Sub-type Article (original research)
DOI 10.18632/oncotarget.9015
Open Access Status DOI
Volume 7
Issue 24
Start page 36474
End page 36488
Total pages 15
Place of publication Albany, NY, United States
Publisher Impact Journals LLC
Collection year 2017
Language eng
Formatted abstract
Telomeric dysfunction is linked to colorectal cancer (CRC) initiation. However, the relationship of normal tissue and tumor telomere lengths with CRC progression, molecular features and prognosis is unclear. Here, we measured relative telomere length (RTL) by real-time quantitative PCR in 90 adenomas (aRTL), 419 stage I-IV CRCs (cRTL) and adjacent normal mucosa (nRTL). Age-adjusted RTL was analyzed against germline variants in telomere biology genes, chromosome instability (CIN), microsatellite instability (MSI), CpG island methylator phenotype (CIMP), TP53, KRAS, BRAF mutations and clinical outcomes. In 509 adenoma or CRC patients, nRTL decreased with advancing age. Female gender, proximal location and the TERT rs2736100 G allele were independently associated with longer age-adjusted nRTL. Adenomas and carcinomas exhibited telomere shortening in 79% and 67% and lengthening in 7% and 15% of cases. Age-adjusted nRTL and cRTL were independently associated with tumor stage, decreasing from adenoma to stage III and leveling out or increasing from stage III to IV, respectively. Cancer MSI, CIMP, TP53, KRAS and BRAF status were not related to nRTL or cRTL. Near-tetraploid CRCs exhibited significantly longer cRTLs than CIN- and aneuploidy CRCs, while cRTL was significantly shorter in CRCs with larger numbers of chromosome breaks. Age-adjusted nRTL, cRTL or cRTL: nRTL ratios were not associated with disease-free or overall survival in stage II/III CRC. Taken together, our data show that both normal mucosa and tumor RTL are independently associated with CRC progression, and highlight divergent associations of CRC telomere length with tumor CIN profiles.
Keyword Telomere length
Colorectal cancer
Chromosome instability
Prognosis
Island Methylator Phenotype
Microsatellite Instability
Carcinoma
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Admin Only - School of Medicine
School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 0 times in Thomson Reuters Web of Science Article
Scopus Citation Count Cited 0 times in Scopus Article
Google Scholar Search Google Scholar
Created: Sun, 10 Jul 2016, 00:22:06 EST by System User on behalf of Learning and Research Services (UQ Library)