Generalised mosaicism for TSC2 mutation in isolated lymphangioleiomyomatosis. Issue 4 (10th October 2019)

• Record Type: Journal Article
• Authors: Ogórek, Barbara; Hamieh, Lana; Lasseter, Kathryn; Bagwe, Shefali; Machado, Tania; Herranz-Ors, Carmen; Thorner, Aaron R.; Nag, Anwesha; Gulleman, Peter; Giannikou, Krinio; Young, Lisa R.; Pujana, Miquel Àngel; Darling, Thomas N.; El-Chemaly, Souheil; Moss, Joel; Henske, Elizabeth P.; Kwiatkowski, David J.
• Is Part Of: European respiratory journal. Volume 54:Issue 4(2019)
• Publication Date: 2019-10-10
• Subjects: Respiratory organs -- Diseases -- Periodicals; Respiration -- Periodicals; 616.2
• DOI: 10.1183/13993003.00938-2019
• Languages: English
• ISSNs: 0903-1936

Abstract

Lymphangioleiomyomatosis (LAM) is a rare, slowly progressive pulmonary disease causing cystic lung destruction and respiratory failure. It affects predominantly premenopausal women, and rarely men. It can occur as a sporadic condition (sporadic LAM) or in association with tuberous sclerosis complex (TSC) [1]. LAM is caused by biallelic inactivation of the tumour suppressor gene TSC2 in LAM cells, which leads to hyperactivation of mammalian target of rapamycin complex (mTORC)1, resulting in anabolism and LAM cell proliferation [2]. Sirolimus and everolimus, mTORC1 allosteric inhibitors, have been shown to retard progression of LAM [3]. Analysis of plasma cell-free DNA from 61 sporadic lymphangioleiomyomatosis (LAM) patients identified generalised mosaicism for a TSC2 mutation in one, suggesting that some sporadic LAM patients are occult generalised mosaics for TSC2 mutations http://bit.ly/2yLr0Ls