Identification of a Cowden syndrome patient with a novel PTEN mutation and establishment of patient-derived induced pluripotent stem cells.

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Publisher: Springer
Document Type: Report; Brief article
Length: 314 words

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Keywords: Cowden syndrome; Phosphatase and tensin homolog deleted on chromosome 10; Phosphatase and tensin homolog deleted on chromosome 10 [delta]; Induced pluripotent stem cells; Feeder- and serum-free culture condition Abstract Cowden syndrome (CS) is an autosomal dominant inherited disorder characterized by multiple hamartomas in various organs such as the mucosa, skin, and gastrointestinal tract. Patients with CS are at high risk for breast and thyroid cancers. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor gene that negatively regulates the AKT pathway, and PTEN mutations are known to be the major causes of this syndrome. However, the pathogenesis of this syndrome has not been clarified. Here, we present a case of a Japanese woman with multiple oral polyps, breast cancer, and thyroid cancer who was clinically diagnosed with CS. We obtained DNA and RNA samples from the patient's peripheral blood mononuclear cells (PBMCs) and buccal mucosa tumor. Next-generation sequencing revealed novel germline mutations (c.1020delT and c.1026G A) in exon 8 of PTEN. Sanger sequencing identified no PTEN transcript from the mutant allele. Furthermore, CS-specific induced pluripotent stem cells (CS-iPSCs) were established from PBMCs of the patient under feeder- and serum-free culture. Compared with healthy PBMCs and iPSCs, both of the CS-derived PBMCs and CS-iPSCs exhibited significantly reduced expression of the PTEN transcript. The transcriptional variant, PTEN[delta], was increased in CS-iPSCs, suggesting that it may be the cause of the disease. Author Affiliation: (1) Department of Oral and Maxillofacial Surgery, Hiroshima University Hospital, Hiroshima, Japan (2) Department of Oral and Maxillofacial Surgery, Hiroshima Prefectural Hospital, Hiroshima, Japan (3) Department of Molecular Oral Medicine and Maxillofacial Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, 734-8553, Hiroshima, Japan (4) School of Medical Sciences, The University of East Asia, Yamaguchi, Japan (b) hamaco@hiroshima-u.ac.jp (f) tetsuok@hiroshima-u.ac.jp Article History: Registration Date: 11/12/2021 Received Date: 10/17/2021 Accepted Date: 11/06/2021 Online Date: 01/03/2022 Byline:

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Gale Document Number: GALE|A691177523