Telomere length and survival in primary cutaneous melanoma patients.
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ABSTRACT:
SUBMITTER: Rachakonda S
PROVIDER: S-EPMC6053393 | biostudies-literature | 2018 Jul
REPOSITORIES: biostudies-literature
Publications
Telomere length and survival in primary cutaneous melanoma patients.
Rachakonda Sivaramakrishna S Srinivas Nalini N Mahmoudpour Seyed Hamidreza SH Garcia-Casado Zaida Z Requena Celia C Traves Victor V Soriano Virtudes V Cardelli Maurizio M Pjanova Dace D Molven Anders A Gruis Nelleke N Nagore Eduardo E Kumar Rajiv R
Scientific reports 20180719 1
Telomere repeats at chromosomal ends, critical to genomic integrity, undergo age-dependent attrition. Telomere length, a polygenic trait, has been associated with risk of several disorders including cancers. In contrast to association of long telomeres with increased risk of several cancers, including melanoma, emerging reports suggest that short telomeres predict poor survival in patients with different cancers. In this study based on 1019 stage I and II cutaneous melanoma patients, we show an ...[more]
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Project description:INTRODUCTION: Recent evidence suggests a link between constitutional telomere length (TL) and cancer risk. Previous studies have suggested that longer telomeres were associated with an increased risk of melanoma and larger size and number of nevi. The goal of this study was to examine whether TL modified the risk of melanoma in melanoma-prone families with and without CDKN2A germline mutations. MATERIALS AND METHODS: We measured TL in blood DNA in 119 cutaneous malignant melanoma (CMM) cases and 208 unaffected individuals. We also genotyped 13 tagging SNPs in TERT. RESULTS: We found that longer telomeres were associated with an increased risk of CMM (adjusted OR?=?2.81, 95% CI?=?1.02-7.72, P?=?0.04). The association of longer TL with CMM risk was seen in CDKN2A- cases but not in CDKN2A+ cases. Among CMM cases, the presence of solar injury was associated with shorter telomeres (P?=?0.002). One SNP in TERT, rs2735940, was significantly associated with TL (P?=?0.002) after Bonferroni correction. DISCUSSION: Our findings suggest that TL regulation could be variable by CDKN2A mutation status, sun exposure, and pigmentation phenotype. Therefore, TL measurement alone may not be a good marker for predicting CMM risk.
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Project description:BackgroundThe outcomes of patients with stage III cutaneous melanoma who undergo complete surgical resection can be highly variable, and estimation of individual risk of disease recurrence and mortality remains imprecise. With recent demonstrations of effective adjuvant targeted and immune checkpoint inhibitor therapy, more precise stratification of patients for costly and potentially toxic adjuvant therapy is needed. We report the utility of pre-operative circulating tumour DNA (ctDNA) in patients with high-risk stage III melanoma.Patients and methodsctDNA was analysed in blood specimens that were collected pre-operatively from 174 patients with stage III melanoma undergoing complete lymph node (LN) dissection. Cox regression analyses were used to evaluate the prognostic significance of ctDNA for distant metastasis recurrence-free survival and melanoma-specific survival (MSS).ResultsThe detection of ctDNA in the discovery and validation cohort was 34% and 33%, respectively, and was associated with larger nodal melanoma deposit, higher number of melanoma involved LNs, more advanced stage and high lactate dehydrogenase (LDH) levels. Detectable ctDNA was significantly associated with worse MSS in the discovery [hazard ratio (HR) 2.11 P < 0.01] and validation cohort (HR 2.29, P = 0.04) and remained significant in a multivariable analysis (HR 1.85, P = 0.04). ctDNA further sub-stratified patients with AJCC stage III substage, with increasing significance observed in more advanced stage melanoma.ConclusionPre-operative ctDNA predicts MSS in high-risk stage III melanoma patients undergoing complete LN dissection, independent of stage III substage. This biomarker may have an important role in determining prognosis and stratifying patients for adjuvant treatment.
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