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  • Author: Polona Le Quesne Stabej x
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Anassuya Ramachandran A Ramachandran, Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland - Grafton Campus, Auckland, 1023, New Zealand

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Polona Le Quesne Stabej P Stabej, University of Auckland - Grafton Campus, Auckland, New Zealand

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Veronica Boyle V Boyle, Te Whatu Ora Health New Zealand Waikato, Hamilton, New Zealand

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Marianne Susan Elston M Elston, Department of Endocrinology, Waikato Hospital, Hamilton, 3240, New Zealand

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Sharon Pattison S Pattison, University of Otago, Dunedin, New Zealand

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Ben Lawrence B Lawrence, Te Whatu Ora Health New Zealand Te Toka Tumai Auckland, Auckland, New Zealand

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Cris Print C Print, Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand

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Although the gene MEN1 has a long association with cancer, its mechanisms of action remain incompletely understood, being both a tumour suppressor in neuroendocrine tumours and an oncogene in leukaemia. The best characterised isoform of the encoded protein, MENIN, is the 610 amino acid MENIN isoform 2. We hypothesise that some of the complexity of MEN1 biology can be attributed to a currently unappreciated contribution of different MENIN isoforms. Through in silico datamining, we show alternative splicing along the entire length of MEN1. Splice junction data suggests that the transcript encoding MENIN isoform 2 is the most abundant in all tissues examined, making a strong argument for this to be the reference transcript/protein isoform of MEN1. We also report novel splicing events, including a novel exon from within intron 7 that is relatively highly expressed in many tissues. These splicing events are predicted to contribute to MENIN diversity by generating isoforms with in-frame insertions, deletions or unique amino termini that, in turn, could have altered interactions with partner proteins. Finally, we have compiled 2574 unique genomic variants reported in MEN1 in somatic and germline databases and have identified several variants that could impact individual MENIN isoforms. We have also collated studies pertinent to MENIN function in the literature and summarise the impact of MEN1 variants on 74 biological variables. We propose a set of 4 MEN1 variants, MENINL22R, MENINH139D, MENINA242V and MENINW436R, that represent a cohort with different biological properties, that should be investigated concurrently to better dissect MENIN function.

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