Abstract:
:Germline deletion of the 3' portion of the Epithelial Cell Adhesion Molecule (EPCAM) gene located 5' upstream of MutS Homolog 2 (MSH2) is a novel mechanism for its inactivation in Lynch syndrome. However, its contribution in Japanese Lynch syndrome patients is poorly understood. Moreover, somatic events inactivating the remaining allele of MSH2 in cancer tissue have not been elucidated in Lynch syndrome patients with such EPCAM deletions. We identified a Japanese Lynch syndrome patient with colon cancer who evidenced germline deletion of a 4130 bp fragment of EPCAM encompassing exons 8 and 9 (c.859-672_*2170del). In normal colonic mucosa, two known fusion-transcripts of EPCAM/MSH2 generated from the rearranged gene were observed and heterozygous methylation of the MSH2 gene promoter was detected. In cancer tissue, dense methylation of MSH2 was observed and MLPA analysis demonstrated somatic deletion of the remaining EPCAM allele including exon 9, indicating that somatic deletion of EPCAM is responsible for complete inactivation of MSH2.
journal_name
Jpn J Clin Oncoljournal_title
Japanese journal of clinical oncologyauthors
Eguchi H,Kumamoto K,Suzuki O,Kohda M,Tada Y,Okazaki Y,Ishida Hdoi
10.1093/jjco/hyv172subject
Has Abstractpub_date
2016-02-01 00:00:00pages
178-84issue
2eissn
0368-2811issn
1465-3621pii
hyv172journal_volume
46pub_type
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