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APC germline variant analysis in the adenomatous polyposis phenotype in Japanese patients

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A Correction to this article was published on 20 December 2021

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Abstract

Background

Familial adenomatous polyposis (FAP), an autosomal dominant disorder characterized by multiple colonic polyps, is caused by a germline pathogenic variant of the APC gene. However, this variant is not detected in up to 30% of patients with the adenomatous polyposis phenotype.

Methods

We performed next-generation sequencing (NGS) to identify the causative genes in FAP patients with 10 or more polyps. For patients in whom the APC germline variant was not able to be identified, we screened for APC mosaicism using high-coverage NGS of APC with DNA from leucocytes and/or frozen tissue.

Results

The pathogenic APC germline variant was found in 93.3%, 71.6%, and 17.1% of patients with profuse-type polyposis, sparse-type polyposis, and oligo-polyposis, respectively. The APC germline variant detection rate in patients with FAP-related diseases was 69.7% for fundic gland polyposis, 79.7% for duodenal adenoma, 94.7% for desmoid tumor, and 71.4% for thyroid cancer, with increasing numbers of extracolonic lesions associated with an increasing APC germline variant detection rate. A mosaic test detected nine patients with APC mosaicism. A comparison of APC-associated polyposis with APC mosaicism showed that patients with APC mosaicism had a low frequency of duodenal adenoma and a family history of colonic polyposis.

Conclusions

We determined the detection rate of the APC germline variant by phenotype and identified APC mosaicism. Genetic testing of FAP patients is important because it can help with surgical decision-making, monitoring, and genetic counseling. Furthermore, genetic testing by NGS proved to be an effective method of detecting APC germline variants.

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Acknowledgements

We are grateful to all the patients and their families and to Mr. James R. Valera for his assistance with editing the manuscript.

Funding

This study was supported in part by the Program for an Integrated Database of Clinical and Genomic Information of the Japan Agency for Medical Research and Development (AMED) [JP18kk0205004] and a grant-in-aid from the Support Project of the Strategic Research Cancer in Private Universities of the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, which was awarded to Saitama Medical University Research Center for Genomic Medicine [S1311002]. This study was also supported in part by a grant from the 2018 Ochiai Memorial Award of Saitama Medical University.

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Authors and Affiliations

  1. Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22, Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan

    Misato Takao & Tatsuro Yamaguchi

  2. Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan

    Misato Takao, Tatsuro Yamaguchi & Hideyuki Ishida

  3. Department of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

    Tatsuro Yamaguchi

  4. Diagnostics and Therapeutics of Intractable Diseases and Intractable Disease Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan

    Hidetaka Eguchi & Yasushi Okazaki

  5. Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan

    Takeshi Yamada

  6. Division of Lower GI Surgery, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan

    Naohiro Tomita

  7. Department of Surgery, Hoshi General Hospital, Koriyama, Japan

    Tadashi Nomizu

  8. Department of Gastrointestinal Tract Surgery, Fukushima Medical University, Fukushima, Japan

    Tomoyuki Momma

  9. Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan

    Tetsuji Takayama

  10. Department of Surgery, Iwakuni Clinical Center, Iwakuni, Japan

    Kohji Tanakaya

  11. Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Saitama, Japan

    Kiwamu Akagi

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  1. Misato Takao
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Correspondence to Tatsuro Yamaguchi.

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Takao, M., Yamaguchi, T., Eguchi, H. et al. APC germline variant analysis in the adenomatous polyposis phenotype in Japanese patients. Int J Clin Oncol 26, 1661–1670 (2021). https://doi.org/10.1007/s10147-021-01946-4

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