Two Distinct Classes of Thymic Tumors in Patients with MEN1 Show LOH at the MEN1 Locus

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Endocr Relat Cancer. 2021 Sep 1:ERC-21-0226.R1. doi: 10.1530/ERC-21-0226. Online ahead of print.


Patients with the multiple endocrine neoplasia type 1 (MEN1) syndrome carry germline heterozygous loss-of-function mutations in the MEN1 gene which predisposes them to the development of various endocrine and non-endocrine tumors. Over 90% of these tumors have been shown to undergo biallelic inactivation of the MEN1 tumor suppressor gene by somatic loss of the wild-type allele resulting in loss of heterozygosity (LOH) at chromosome 11q13, the MEN1 gene locus. An uncommon manifestation of MEN1 is thymic neuroendocrine tumor (thymic NET), also referred to as thymic carcinoid, which in MEN1 patients is a major cause of mortality. In contrast to the other frequent NETs in MEN1 patients (pancreas, parathyroid, pituitary), LOH at the MEN1 locus has not been demonstrated in MEN1-associated thymic tumors. Therefore, it is generally thought that thymic tumor development in MEN1 patients is dependent on other somatic molecular events rather than a second hit to the MEN1 gene and its pathogenesis is largely unknown. The lack of knowledge of its pathogenesis limits the ability to explore therapies directed at this tumor, which is the most aggressive of all MEN1-associated tumors. The goal of this study was to investigate the molecular events contributing to thymic tumor development in our well-characterized cohort of MEN1 patients by evaluating LOH at the MEN1 locus and by utilizing transcriptomics to identify possible molecular hits that may lead to tumor development and could be considered for targeted therapy.

PMID:34515662 | DOI:10.1530/ERC-21-0226