Familial adenomatous patients with desmoid tumours show increased expression of miR-34a in serum and high levels in tumours
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https://doi.org/10.18632/oncoscience.312
Sarah-Jane Walton1,†, Amy Lewis2,†,Rosemary Jeffery2, Hannah Thompson2, Roger Feakins3, Eleni Giannoulatou4,5, Christopher Yau6, James O. Lindsay2, Susan K. Clark1*, Andrew Silver2,*
1 The Polyposis Registry, St Mark’s Hospital, Watford Road, Harrow, HA1 3UJ, United Kingdom and Department of Surgery and Cancer, Imperial College London, United Kingdom
2 Centre for Genomics and Child Health and National Centre for Bowel Research and Surgical Innovation, Barts and The London School of Medicine & Dentistry, London, United Kingdom
3 Department of Histopathology, The Royal London Hospital, London, United Kingdom
4 Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia
5 The University of New South Wales, NSW, Australia
6 Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
† Co-first authors
Correspondence:
Susan K. Clark, email:
Andrew Silver, email:
Keywords: desmoid tumour, familial adenomatous polyposis, microRNA, miRNA-34a-5p, Wnt pathway
Received: April 04, 2016 Accepted: June 03, 2016 Published: June 11, 2016
Abstract
Familial adenomatous polyposis (FAP) is rare affecting 1 in 10,000 people and a subset (10%) are at risk of myofibroblastic desmoid tumours (DTs) after colectomy to prevent cancer. DTs are a major cause of morbidity and mortality. The absence of markers to monitor progression and a lack of treatment options are significant limitations to clinical management. We investigated microRNAs (miRNA) levels in DTs and serum using expression array analysis on two independent cohorts of FAP patients (total, n=24). Each comprised equal numbers of patients who had formed DTs (cases) and those who had not (controls). All controls had absence of DTs confirmed by clinical and radiological assessment over at least three years postcolectomy. Technical qPCR validation was performed using an expanded cohort (29 FAP patients; 16 cases and 13 controls). The most significant elevated serum miRNA marker of DTs was miR-34a-5p and in-situ hybridisation (ISH) showed most DTs analysed (5/6) expressed miRNA-34a-5p. Exome sequencing of tumour and matched germline DNA did not detect mutations within the miR-34a-5p transcript sites or 3’-UTR of target genes that would alter functional miRNA activity. In conclusion, miR-34a-5p is a potential circulatory marker and therapy target. A large prospective world-wide multi-centre study is now warranted.
