Identification of a founder EPCAM deletion in Spanish Lynch syndrome families. (26th April 2013)

• Record Type: Journal Article
• Authors: Mur, P.; Pineda, M.; Romero, A.; del Valle, J.; Borràs, E.; Canal, A.; Navarro, M.; Brunet, J.; Rueda, D.; Ramón y Cajal, T.; Lázaro, C.; Caldés, T.; Blanco, I.; Soto, J.L.; Capellá, G.
• Is Part Of: Clinical genetics. Volume 85:Number 3(2014:Mar.)
• Page Start: 260
• Page End: 266
• Publication Date: 2013-04-26
• Subjects: Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.12152
• Languages: English
• ISSNs: 0009-9163

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Germline deletions at the 3′‐end of <italic>EPCAM</italic> have been involved in the etiology of Lynch syndrome (LS). The aim of this study was to characterize at the molecular level Spanish families harboring <italic>EPCAM</italic> deletions. Non‐commercial multiplex ligation‐dependent probe amplification (MLPA) probes and long‐range polymerase chain reaction (PCR) amplification were used to characterize each deletion. Haplotyping was performed by analyzing eight microsatellite markers and five <italic>MSH2</italic>single nucleotide polymorphisms (SNPs). Methylation of <italic>MSH2</italic> was analyzed by methylation specific‐MLPA. Tumors diagnosed in seven Spanish families harboring <italic>EPCAM</italic> deletions were almost exclusively colorectal. Mosaicism in <italic>MSH2</italic> methylation was observed in <italic>EPCAM</italic> deletion carrier samples, being average methylation levels higher in normal colon and colorectal tumors (27.6% and 31.1%), than in lymphocytes and oral mucosa (1.1% and 0.7%). Three families shared the deletion c.858 + 2568_*4596del, with a common haplotype comprising 9.9 Mb. In two families the novel <italic>EPCAM</italic> deletion c.858 + 2488_*7469del was identified. This study provides knowledge on the clinical and molecular characteristics of mosaic <italic>MSH2</italic> epimutations. The identification of an <italic>EPCAM</italic> founder mutation has useful implications for the molecular diagnosis of LS in Spain.</p> </abstract>