Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular and Clinical Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 2049-9450 Online ISSN: 2049-9469
Journal Cover
February-2022 Volume 16 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
February-2022 Volume 16 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

COL17A1 germline variant p.Ser1029Ala and mucosal malignant melanoma: An autopsy study

  • Authors:
    • Daike Tong
    • Masashi Tanaka
    • Hidetaka Eguchi
    • Yasushi Okazaki
    • Masaaki Muramatsu
    • Tomio Arai
  • View Affiliations / Copyright

    Affiliations: Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113‑8510, Japan, Department of Neurology, Graduate School of Medicine, Juntendo University, Tokyo 113‑8421, Japan, Diagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Tokyo 113‑8421, Japan, Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Tokyo 173‑0015, Japan
    Copyright: © Tong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 32
    |
    Published online on: December 14, 2021
       https://doi.org/10.3892/mco.2021.2465
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Collagen type XVII α1 (COL17A1) encodes a hemidesmosomal protein at the epidermal‑dermal junction and its variants are implicated in blistering skin diseases. Recent experiments in rodents revealed that Col17a1 has critical roles in stem cells of epidermal origin and in melanoma carcinogenesis. In the present study, it was investigated whether germline variants in COL17A1 are associated with skin cancer and other cancer types using indexed consecutive autopsy cases from the Japanese Geriatric Single Nucleotide Polymorphism database (n=2,343; mean age, 80 years). The database included 12 patients with skin cancer. A total of 53 COL17A1 missense variants on an exome chip were analyzed. One variant, p.Ser1029Ala (rs118166857), which had a minor allele frequency of 1.0%, exhibited a nominal positive sign of association with skin cancer [Fisher's exact P=0.002, odds ratio (OR)=16.93, 95% CI: 4.44‑64.64]. This variant was detected in 2/2 patients with mucosal malignant melanoma (mMM) and 1/3 patients with extramammary Paget's disease, and in none of the patients with non‑melanoma cancer, e.g., squamous cell and basal cell carcinoma. Other cancer types were searched in the database and the p.Ser1029Ala variant was indicated to be nominally associated with breast cancer (P=0.006, OR=4.17, 95% CI: 1.72‑10.11). In the two mMM cases, targeted exome sequencing of 55 cancer‑predisposing genes (including tumor protein 53, BRCA1/2 and mismatch repair genes) detected no apparent pathogenic variants, but revealed variants of unknown significance in axin 2, DNA directed polymerase ζ catalytic subunit and contactin 6. Since COL17A1 provides a niche for melanocyte stem cells, it was hypothesized that the p.Ser1029Ala variant in the COL17A1 ectodomain may affect the microenvironment, e.g., the cell competition. This is a working hypothesis generated from human autopsy cases and warrants further epidemiological and molecular biological validation.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Mikkelsen LH, Larsen AC, von Buchwald C, Drzewiecki KT, Prause JU and Heegaard S: Mucosal malignant melanoma-a clinical, oncological, pathological and genetic survey. APMIS. 124:475–486. 2016.PubMed/NCBI View Article : Google Scholar

2 

Yde SS, Sjoegren P, Heje M and Stolle LB: Mucosal melanoma: A literature review. Curr Oncol Rep. 20(28)2018.PubMed/NCBI View Article : Google Scholar

3 

Nishie W: Collagen XVII processing and blistering skin diseases. Acta Derm Venereol. 12(adv00054)2020.PubMed/NCBI View Article : Google Scholar

4 

Krenacs T, Kiszner G, Stelkovics E, Balla P, Teleki I, Nemeth I, Varga E, Korom I, Barbai T, Plotar V, et al: Collagen XVII is expressed in malignant but not in benign melanocytic tumors and it can mediate antibody induced melanoma apoptosis. Histochem Cell Biol. 138:653–667. 2012.PubMed/NCBI View Article : Google Scholar

5 

Hwang BJ, Zhang Y, Brozowski JM, Liu Z, Burette S, Lough K, Smith CC, Shan Y, Chen J, Li N, et al: The dysfunction of BP180/collagen XVII in keratinocytes promotes melanoma progression. Oncogene. 38:7491–7503. 2019.PubMed/NCBI View Article : Google Scholar

6 

Sawabe M, Arai T, Kasahara I, Esaki Y, Nakahara K, Hosoi T, Orimo H, Takubo K, Murayama S and Tanaka N: Tokyo Metropolitan Geriatric Medical Center; Japan Science and Technology Agency. Developments of geriatric autopsy database and Internet-based database of Japanese single nucleotide polymorphisms for geriatric research (JG-SNP). Mech Ageing Dev. 125:547–552. 2004.PubMed/NCBI View Article : Google Scholar

7 

Yamada M, Sato N, Ikeda S, Arai T, Sawabe M, Mori S, Yamada Y, Muramatsu M and Tanaka M: Association of the chromodomain helicase DNA-binding protein 4 (CHD4) missense variation p.D140E with cancer: Potential interaction with smoking. Genes Chromosomes Cancer. 54:122–128. 2015.PubMed/NCBI View Article : Google Scholar

8 

Eguchi H and Okazaki Y: Next-generation sequencing for genetic diagnosis of hereditary colorectal cancer and polyposis syndrome. In: Recent Advances in the Treatment of Colorectal Cancer. Ishida H (eds). Springer, pp115-125, 2019.

9 

Tadaka S, Hishinuma E, Komaki S, Motoike IN, Kawashima J, Saigusa D, Inoue J, Takayama J, Okamura Y, Aoki Y, et al: jMorp updates in 2020: Large enhancement of multi-omics data resources on the general Japanese population. Nucleic Acids Res. 49:D536–D544. 2021.PubMed/NCBI View Article : Google Scholar

10 

Adzhubei I, Jordan DM and Sunyaev SR: Predicting functional effect of human missense mutations using PolyPhen-2. Curr Protoc Hum Genet Chapter 7: Unit7.20, 2013.

11 

Peng J, Han F, Yang T, Sun J, Guan W and Guo X: Primary malignant melanoma of the lung: A case report and literature review. Medicine (Baltimore). 96(e8772)2017.PubMed/NCBI View Article : Google Scholar

12 

Tomizuka T, Namikawa K and Higashi T: Characteristics of melanoma in Japan: A nationwide registry analysis 2011-2013. Melanoma Res. 27:492–497. 2017.PubMed/NCBI View Article : Google Scholar

13 

Carvajal RD, Spencer SA and Lydiatt W: Mucosal melanoma: A clinically and biologically unique disease entity. J Natl Compr Canc Netw. 10:345–356. 2012.PubMed/NCBI View Article : Google Scholar

14 

Kamaguchi M and Iwata H: The diagnosis and blistering mechanisms of mucous membrane pemphigoid. Front Immunol. 24(34)2019.PubMed/NCBI View Article : Google Scholar

15 

Pogorzelska-Dyrbus J and Szepietowski JC: Adhesion molecules in non-melanoma skin cancers: A comprehensive review. In Vivo. 35:1327–1336. 2021.PubMed/NCBI View Article : Google Scholar

16 

Tanimura S, Tadokoro Y, Inomata K, Binh NT, Nishie W, Yamazaki S, Nakauchi H, Tanaka Y, McMillan JR, Sawamura D, et al: Hair follicle stem cells provide a functional niche for melanocyte stem cells. Cell Stem Cell. 8:177–187. 2011.PubMed/NCBI View Article : Google Scholar

17 

Liu N, Matsumura H, Kato T, Ichinose S, Takada A, Namiki T, Asakawa K, Morinaga H, Mohri Y, De Arcangelis A, et al: Stem cell competition orchestrates skin homeostasis and ageing. Nature. 568:344–350. 2019.PubMed/NCBI View Article : Google Scholar

18 

Natsuga K, Watanabe M, Nishie W and Shimizu H: Life before and beyond blistering: The role of collagen XVII in epidermal physiology. Exp Dermatol. 28:1135–1141. 2019.PubMed/NCBI View Article : Google Scholar

19 

Vishwakarma M and Piddini E: Outcompeting cancer. Nat Rev Cancer. 20:187–198. 2020.PubMed/NCBI View Article : Google Scholar

20 

Ferrari AJ, Drapkin R and Gogna R: Cell fitness: More than push-ups. Int J Mol Sci. 22(518)2021.PubMed/NCBI View Article : Google Scholar

21 

Yodsurang V, Tanikawa C, Miyamoto T, Lo PHY, Hirata M and Matsuda K: Identification of a novel p53 target, COL17A1, that inhibits breast cancer cell migration and invasion. Oncotarget. 8:55790–55803. 2017.PubMed/NCBI View Article : Google Scholar

22 

Lothong M, Sakares W, Rojsitthisak P, Tanikawa C, Matsuda K and Yodsurang V: Collagen XVII inhibits breast cancer cell proliferation and growth through deactivation of the AKT/mTOR signaling pathway. PLoS One. 16(e0255179)2021.PubMed/NCBI View Article : Google Scholar

23 

Kozawa K, Sekai M, Ohba K, Ito S, Sako H, Maruyama T, Kakeno M, Shirai T, Kuromiya K, Kamasaki T, et al: The CD44/COL17A1 pathway promotes the formation of multilayered, transformed epithelia. Curr Biol. 26:3086–3097.e7. 2021.PubMed/NCBI View Article : Google Scholar

24 

Martin SK and Wood RD: DNA polymerase ζ in DNA replication and repair. Nucleic Acids Res. 19:8348–8361. 2019.PubMed/NCBI View Article : Google Scholar

25 

Chae YK, Anker JF, Carneiro BA, Chandra S, Kaplan J, Kalyan A, Santa-Maria CA, Platanias LC and Giles FJ: Genomic landscape of DNA repair genes in cancer. Oncotarget. 26:23312–23321. 2016.PubMed/NCBI View Article : Google Scholar

26 

Song L, McNeil EM, Ritchie AM, Astell KR, Gourley C and Melton DW: Melanoma cells replicate through chemotherapy by reducing levels of key homologous recombination protein RAD51 and increasing expression of translesion synthesis DNA polymerase ζ. BMC Cancer. 18(864)2017.PubMed/NCBI View Article : Google Scholar

27 

Arivazhagan R, Lee J, Bayarsaikhan D, Kwak P, Son M, Byun K, Salekdeh GH and Lee B: MicroRNA-340 inhibits the proliferation and promotes the apoptosis of colon cancer cells by modulating REV3L. Oncotarget. 26:5155–5168. 2017.PubMed/NCBI View Article : Google Scholar

28 

Strong AM, Setaluri V and Spiegelman VS: MicroRNA-340 as a modulator of RAS-RAF-MAPK signaling in melanoma. Arch Biochem Biophys. 1:118–124. 2014.PubMed/NCBI View Article : Google Scholar

29 

Julius MA, Schelbert B, Hsu W, Fitzpatrick E, Jho E, Fagotto F, Costantini F and Kitajewski J: Domains of axin and disheveled required for interaction and function in wnt signaling. Biochem Biophys Res Commun. 276:1162–1169. 2000.PubMed/NCBI View Article : Google Scholar

30 

Ikeda S, Kishida S, Yamamoto H, Murai H, Koyama S and Kikuchi A: Axin, a n9gative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin. EMBO J. 17:1371–1384. 1998.PubMed/NCBI View Article : Google Scholar

31 

Castiglia D, Bernardini S, Alvino E, Pagani E, Luca ND, Falcinelli S, Pacchiarotti A, Bonmassar E, Zambruno G and D'Atri S: Concomitant activation of Wnt pathway and loss of mismatch repair function in human melanoma. Genes Chromosomes Cancer. 47:614–624. 2008.PubMed/NCBI View Article : Google Scholar

32 

Smith AA, Li J, Liu B, Hunter D, Pyles M, Gillette M, Dhamdhere GR, Abo A, Oro A and Helms JA: Activating hair follicle stem cells via R-spondin2 to stimulate hair growth. J Invest Dermatol. 136:1549–1558. 2016.PubMed/NCBI View Article : Google Scholar

33 

Du Y, Shao H, Moller M, Prokupets R, Tse YT and Liu ZJ: Intracellular notch1 signaling in cancer-associated fibroblasts dictates the plasticity and stemness of melanoma stem/initiating cells. Stem Cells. 37:865–875. 2019.PubMed/NCBI View Article : Google Scholar

34 

Chen J, Wu F, Shi Y, Yang D, Xu M, Lai Y and Liu Y: Identification of key candidate genes involved in melanoma metastasis. Mol Med Rep. 20:903–914. 2019.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Tong D, Tanaka M, Eguchi H, Okazaki Y, Muramatsu M and Arai T: COL17A1 germline variant p.Ser1029Ala and mucosal malignant melanoma: An autopsy study. Mol Clin Oncol 16: 32, 2022.
APA
Tong, D., Tanaka, M., Eguchi, H., Okazaki, Y., Muramatsu, M., & Arai, T. (2022). COL17A1 germline variant p.Ser1029Ala and mucosal malignant melanoma: An autopsy study. Molecular and Clinical Oncology, 16, 32. https://doi.org/10.3892/mco.2021.2465
MLA
Tong, D., Tanaka, M., Eguchi, H., Okazaki, Y., Muramatsu, M., Arai, T."COL17A1 germline variant p.Ser1029Ala and mucosal malignant melanoma: An autopsy study". Molecular and Clinical Oncology 16.2 (2022): 32.
Chicago
Tong, D., Tanaka, M., Eguchi, H., Okazaki, Y., Muramatsu, M., Arai, T."COL17A1 germline variant p.Ser1029Ala and mucosal malignant melanoma: An autopsy study". Molecular and Clinical Oncology 16, no. 2 (2022): 32. https://doi.org/10.3892/mco.2021.2465
Copy and paste a formatted citation
x
Spandidos Publications style
Tong D, Tanaka M, Eguchi H, Okazaki Y, Muramatsu M and Arai T: COL17A1 germline variant p.Ser1029Ala and mucosal malignant melanoma: An autopsy study. Mol Clin Oncol 16: 32, 2022.
APA
Tong, D., Tanaka, M., Eguchi, H., Okazaki, Y., Muramatsu, M., & Arai, T. (2022). COL17A1 germline variant p.Ser1029Ala and mucosal malignant melanoma: An autopsy study. Molecular and Clinical Oncology, 16, 32. https://doi.org/10.3892/mco.2021.2465
MLA
Tong, D., Tanaka, M., Eguchi, H., Okazaki, Y., Muramatsu, M., Arai, T."COL17A1 germline variant p.Ser1029Ala and mucosal malignant melanoma: An autopsy study". Molecular and Clinical Oncology 16.2 (2022): 32.
Chicago
Tong, D., Tanaka, M., Eguchi, H., Okazaki, Y., Muramatsu, M., Arai, T."COL17A1 germline variant p.Ser1029Ala and mucosal malignant melanoma: An autopsy study". Molecular and Clinical Oncology 16, no. 2 (2022): 32. https://doi.org/10.3892/mco.2021.2465
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team