Journal article
Recurrent loss of heterozygosity correlates with clinical outcome in pancreatic neuroendocrine cancer
B Lawrence, C Blenkiron, K Parker, P Tsai, S Fitzgerald, P Shields, T Robb, ML Yeong, N Kramer, S James, M Black, V Fan, N Poonawala, P Yap, E Coats, B Woodhouse, R Ramsaroop, M Yozu, B Robinson, K Henare Show all
Npj Genomic Medicine | SPRINGERNATURE | Published : 2018
Abstract
Pancreatic neuroendocrine tumors (pNETs) are uncommon cancers arising from pancreatic islet cells. Here we report the analysis of gene mutation, copy number, and RNA expression of 57 sporadic well-differentiated pNETs. pNET genomes are dominated by aneuploidy, leading to concordant changes in RNA expression at the level of whole chromosomes and chromosome segments. We observed two distinct patterns of somatic pNET aneuploidy that are associated with tumor pathology and patient prognosis. Approximately 26% of the patients in this series had pNETs with genomes characterized by recurrent loss of heterozygosity (LoH) of 10 specific chromosomes, accompanied by bi-allelic MEN1 inactivation and gen..
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Funding Acknowledgements
We thank all patients who donated samples and clinical data to our study. We also thank Stefan Bohlander (University of Auckland) for his help with genomic data analysis and interpretation, Ruellyn Cockcroft, Simon Fu, Rebecca Jones and Ole Schmeidel (Auckland DHB), Dean Harris (Canterbury DHB), Richard Issacs (Mid-Central DHB, and Jeremy Rossaak (Bay of Plenty DHB) for clinical input, Siobhan Conroy and Avril Hull of the Unicorn Foundation for coordinating patient input and support, Melissa Firth for input to the Register set up, Maui Hudson and Helen Wihongi for cultural advice and David Jansen for help with translation of key aspects of our project into Te Reo Ma-ori, Malcolm Legget for ongoing advice as Chair of the Translational Medicine Trust, Thierry Lints for thorough review of the manuscript, Ramon Gallego, Aaron Jeffs, Purvi Kakadiya, Rebecca Laurie, John Markham, Les McNoe, John Pearson, Thalanie Purdy, Puja Sharma, Bruce Tsai, Nic Waddell, and Liam Williams for help in the design and interpretation of laboratory studies. This work was financially supported by the Translational Medicine Trust. This work was financially supported by the New Zealand Translational Medicine Trust, Callaghan Innovation, Genesis Oncology Trust, Newmarket Rotary Trusts, Genomics Aotearoa, and the University of Auckland Genomics Into Medicine initiative.