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
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
September-2025 Volume 30 Issue 3

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
September-2025 Volume 30 Issue 3

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
Case Report Open Access

A FANCD2 gene mutation case analysis providing potential insights into the molecular mechanisms of gastric adenocarcinoma: A case report

  • Authors:
    • Kexin Zheng
    • Fengying Du
    • Yaodong Sang
    • Kangdi Dong
    • Kun Xiao
    • Ronghua Zhang
    • Changqing Jing
    • Liang Shang
    • Leping Li
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterological Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, P.R. China, Department of Digestive Tumour Translational Medicine, Engineering Laboratory of Shandong Province, Shandong Provincial Hospital, Jinan, Shandong 250021, P.R. China, Department of Digestive Tumour Translational Medicine, Engineering Laboratory of Shandong Province, Shandong Provincial Hospital, Jinan, Shandong 250021, P.R. China, Department of Gastroenterological Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, P.R. China
    Copyright: © Zheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 422
    |
    Published online on: July 3, 2025
       https://doi.org/10.3892/ol.2025.15168
  • 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

The present case report describes the potential role of Fanconi anaemia complementation group D2 (FANCD2) gene mutations in poorly differentiated gastric adenocarcinoma. A 32‑year‑old male patient was found to have poorly differentiated adenocarcinoma by gastrointestinal endoscopy and pathological examination confirmed this diagnosis. The N1378Sfs*5 mutation in the FANCD2 gene was identified by gene sequencing of postoperative tissues. FANCD2 gene mutation leads to the instability and abnormal function of FANCD2 protein, which may promote the development and progression of gastric cancer. Bioinformatics was used to analyze gastric cancer data and identified key DNA repair genes and FANCD2's core pathways via gene set enrichment analysis and a protein‑protein interactin network. FANCD2 gene mutation not only affects the DNA repair process but may also be involved in cell cycle regulation and apoptosis pathway, which plays an important role in the development of gastric adenocarcinoma. As FANCD2 gene mutation may be a risk factor for familial gastric cancer, genetic counselling services and early screening programs for FANCD2 gene mutation should be developed, with a special focus on individuals with a family history of gastric cancer.
View Figures

Figure 1

Patient case data. (A) CT image of
the stomach (the white arrows indicate the gastric cancer site).
(B) Surgical specimen (the white arrows indicate the gastric cancer
site). (C) Postoperative pathology (H&E staining) - at 200 µm,
active nuclear division is visible, and at 50 µm, signet ring cells
are visible. (D) FANCD2 immunohistochemical staining results from
the postoperative pathology of the patient; no FANCD2 staining was
observed at both 200 and 50 µm magnifications. Left IHC images, 200
µm; right IHC images, 50 µm. FANCD2, Fanconi anaemia
complementation group D2; IHC, immunohistochemistry.

Figure 2

FANCD2 mutation in the 32-year-old
male patient with gastric adenocarcinoma. The light blue arrows
indicate the direction of DNA transcription, the dark blue arrows
represent the direction of the flowchart and the red arrows point
to the location of mutations. FANCD2, Fanconi anaemia
complementation group D2; STAD, stomach adenocarcinoma; Ala,
Alanine; Met, Methionine; Leu, Leucine; Thr, Threonine; Asn,
Asparagine; Ser, Serine; Gln, Glutamine.

Figure 3

FANCD2 is involved in the DNA damage
repair pathway. GSEA analysis of (A) KEGG pathways, (B) REACTOME
pathways, (C) HALLMARK pathways and (D) GO-BP pathways based on
FANCD2 expression levels in gastric cancer samples from the ACRG
cohort. GSEA analysis of (E) KEGG pathways, (F) REACTOME pathways,
(G) HALLMARK pathways and (H) GO-BP pathways based on FANCD2
expression levels in gastric cancer samples from the TCGA-STAD
cohort. (I) Interaction network of the top 10 key genes in DNA
repair and FANCD2. (J) Correlation coefficient matrix of the top 10
key genes in DNA repair and FANCD2 (lower left for the ACRG cohort,
upper right for the TCGA-STAD cohort). The coloured scale bar
represents the correlation coefficient, with red representing a
negative correlation and blue representing a positive correlation,
and the darker the color, the stronger the correlation. (K)
Functional enrichment chord diagram of the top 10 key genes in DNA
repair and FANCD2. The coloured scale bar represents the size of
the P-value, with a lighter colour indicating a smaller P-value.
FANCD2, Fanconi anaemia complementation group D2; GSEA, Gene Set
Enrichment Analysis; KEGG, Kyoto Encyclopaedia of Genes and
Genomes; REACTOME, Reaction and complex transformation or molecular
environment; HALLMARK, Hallmark Gene Sets; GO-BP, Gene
Ontology-Biological Process; ACRG, Asian Cancer Research Group;
TCGA, The Cancer Genome Atlas Program; STAD, stomach
adenocarcinoma; RAD18, RAD18 E3 ubiquitin protein ligase; RRM1,
ribonucleotide reductase catalytic subunit M1; MCM, minichromosome
maintenance protein; CDC45, cell division cycle 45; TOP2B, DNA
topoisomerase II beta; RUVBL1, RuvB like AAA ATPase 1; PPP4C,
protein phosphatase 4 catalytic subunit; FOXM1, forkhead box M1;
PLK1, polo-like kinase 1; ES, enrichment score; NP, normalized
P-value.
View References

1 

Ganesh K and Massagué J: Targeting metastatic cancer. Nat Med. 27:34–44. 2021. View Article : Google Scholar : PubMed/NCBI

2 

Smyth EC, Nilsson M, Grabsch HI, van Grieken NC and Lordick F: Gastric cancer. Lancet. 396:635–648. 2020. View Article : Google Scholar

3 

Guan WL, He Y and Xu RH: Gastric cancer treatment: Recent progress and future perspectives. J Hematol Oncol. 16:572023. View Article : Google Scholar

4 

Lachaud C, Moreno A, Marchesi F, Toth R, Blow JJ and Rouse J: Ubiquitinated Fancd2 recruits Fan1 to stalled replication forks to prevent genome instability. Science. 351:846–849. 2016. View Article : Google Scholar : PubMed/NCBI

5 

Nalepa G and Clapp DW: Fanconi anaemia and cancer: An intricate relationship. Nat Rev Cancer. 18:168–185. 2018. View Article : Google Scholar : PubMed/NCBI

6 

Du F, Peng L, Wang Q, Dong K, Pei W, Zhuo H, Xu T, Jing C, Li L and Zhang J: CCDC12 promotes tumor development and invasion through the Snail pathway in colon adenocarcinoma. Cell Death Dis. 13:1872022. View Article : Google Scholar : PubMed/NCBI

7 

Ajani JA, D'Amico TA, Bentrem DJ, Chao J, Cooke D, Corvera C, Das P, Enzinger PC, Enzler T, Fanta P, et al: Gastric cancer, version 2.2022, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 20:167–192. 2022. View Article : Google Scholar : PubMed/NCBI

8 

Oh SC, Sohn BH, Cheong JH, Kim SB, Lee JE, Park KC, Lee SH, Park JL, Park YY, Lee HS, et al: Clinical and genomic landscape of gastric cancer with a mesenchymal phenotype. Nat Commun. 9:17772018. View Article : Google Scholar : PubMed/NCBI

9 

Stillman B: Smart machines at the DNA replication fork. Cell. 78:725–728. 1994. View Article : Google Scholar

10 

Li GM: Mechanisms and functions of DNA mismatch repair. Cell Res. 18:85–98. 2008. View Article : Google Scholar : PubMed/NCBI

11 

Kraemer KH, Patronas NJ, Schiffmann R, Brooks BP, Tamura D and DiGiovanna JJ: Xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome: A complex genotype-phenotype relationship. Neuroscience. 145:1388–1396. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Saldivar JS, Wu X, Follen M and Gershenson D: Nucleotide excision repair pathway review I: Implications in ovarian cancer and platinum sensitivity. Gynecol Oncol. 107 (Suppl 1):S56–S71. 2007. View Article : Google Scholar

13 

Turczynski S, Titeux M, Pironon N and Hovnanian A: Antisense-mediated exon skipping to reframe transcripts. Methods Mol Biol. 867:221–238. 2012. View Article : Google Scholar

14 

Badra Fajardo N, Taraviras S and Lygerou Z: Fanconi anemia proteins and genome fragility: unraveling replication defects for cancer therapy. Trends Cancer. 8:467–481. 2022. View Article : Google Scholar : PubMed/NCBI

15 

Hsieh CC, Hsu SH, Lin CY, Liaw HJ, Li TW, Jiang KY, Chiang NJ, Chen SH, Lin BW, Chen PC, et al: CHK2 activation contributes to the development of oxaliplatin resistance in colorectal cancer. Br J Cancer. 127:1615–1628. 2022. View Article : Google Scholar : PubMed/NCBI

16 

Webster ALH, Sanders MA, Patel K, Dietrich R, Noonan RJ, Lach FP, White RR, Goldfarb A, Hadi K, Edwards MM, et al: Genomic signature of Fanconi anaemia DNA repair pathway deficiency in cancer. Nature. 612:495–502. 2022. View Article : Google Scholar : PubMed/NCBI

17 

Fagerholm R, Sprott K, Heikkinen T, Bartkova J, Heikkilä P, Aittomäki K, Bartek J, Weaver D, Blomqvist C and Nevanlinna H: Overabundant FANCD2, alone and combined with NQO1, is a sensitive marker of adverse prognosis in breast cancer. Ann Oncol. 24:2780–2785. 2013. View Article : Google Scholar

18 

Titeux M, Turczynski S, Pironon N and Hovnanian A: Antisense-mediated splice modulation to reframe transcripts. Methods Mol Biol. 1828:531–552. 2018. View Article : Google Scholar

19 

Steeland S, Timmermans S, Van Ryckeghem S, Hulpiau P, Saeys Y, Van Montagu M, Vandenbroucke RE and Libert C: Efficient analysis of mouse genome sequences reveal many nonsense variants. Proc Natl Acad Sci USA. 113:5670–5675. 2016. View Article : Google Scholar : PubMed/NCBI

20 

Litchfield K, Reading JL, Lim EL, Xu H, Liu P, Al-Bakir M, Wong YNS, Rowan A, Funt SA, Merghoub T, et al: Escape from nonsense-mediated decay associates with anti-tumor immunogenicity. Nat Commun. 11:38002020. View Article : Google Scholar : PubMed/NCBI

21 

Lemonidis K, Arkinson C, Rennie ML and Walden H: Mechanism, specificity, and function of FANCD2-FANCI ubiquitination and deubiquitination. FEBS J. 289:4811–4829. 2022. View Article : Google Scholar : PubMed/NCBI

22 

Zhang J, Dewar JM, Budzowska M, Motnenko A, Cohn MA and Walter JC: DNA interstrand cross-link repair requires replication-fork convergence. Nat Struct Mol Biol. 22:242–247. 2015. View Article : Google Scholar

23 

Lu Z, Mao W, Yang H, Santiago-O'Farrill JM, Rask PJ, Mondal J, Chen H, Ivan C, Liu X, Liu CG and Xi Y: SIK2 inhibition enhances PARP inhibitor activity synergistically in ovarian and triple-negative breast cancers. J Clin Invest. 132:e1464712022. View Article : Google Scholar

24 

Liu TX, Howlett NG, Deng M, Langenau DM, Hsu K, Rhodes J, Kanki JP, D'Andrea AD and Look AT: Knockdown of zebrafish Fancd2 causes developmental abnormalities via p53-dependent apoptosis. Dev Cell. 5:903–914. 2003. View Article : Google Scholar

25 

Sun S, He H, Ma Y, Xu J, Chen G, Sun Y and Xiong X: Inactivation of ribosomal protein S27-like impairs DNA interstrand cross-link repair by destabilization of FANCD2 and FANCI. Cell Death Dis. 11:8522020. View Article : Google Scholar : PubMed/NCBI

26 

Miao H, Ren Q, Li H, Zeng M, Chen D, Xu C, Chen Y and Wen Z: Comprehensive analysis of the autophagy-dependent ferroptosis-related gene FANCD2 in lung adenocarcinoma. BMC Cancer. 22:2252022. View Article : Google Scholar : PubMed/NCBI

27 

Emam A, Wu X, Xu S, Wang L, Liu S and Wang B: Stalled replication fork protection limits cGAS-STING and P-body-dependent innate immune signalling. Nat Cell Biol. 24:1154–1164. 2022. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zheng K, Du F, Sang Y, Dong K, Xiao K, Zhang R, Jing C, Shang L and Li L: A FANCD2 gene mutation case analysis providing potential insights into the molecular mechanisms of gastric adenocarcinoma: A case report. Oncol Lett 30: 422, 2025.
APA
Zheng, K., Du, F., Sang, Y., Dong, K., Xiao, K., Zhang, R. ... Li, L. (2025). A FANCD2 gene mutation case analysis providing potential insights into the molecular mechanisms of gastric adenocarcinoma: A case report. Oncology Letters, 30, 422. https://doi.org/10.3892/ol.2025.15168
MLA
Zheng, K., Du, F., Sang, Y., Dong, K., Xiao, K., Zhang, R., Jing, C., Shang, L., Li, L."A FANCD2 gene mutation case analysis providing potential insights into the molecular mechanisms of gastric adenocarcinoma: A case report". Oncology Letters 30.3 (2025): 422.
Chicago
Zheng, K., Du, F., Sang, Y., Dong, K., Xiao, K., Zhang, R., Jing, C., Shang, L., Li, L."A FANCD2 gene mutation case analysis providing potential insights into the molecular mechanisms of gastric adenocarcinoma: A case report". Oncology Letters 30, no. 3 (2025): 422. https://doi.org/10.3892/ol.2025.15168
Copy and paste a formatted citation
x
Spandidos Publications style
Zheng K, Du F, Sang Y, Dong K, Xiao K, Zhang R, Jing C, Shang L and Li L: A FANCD2 gene mutation case analysis providing potential insights into the molecular mechanisms of gastric adenocarcinoma: A case report. Oncol Lett 30: 422, 2025.
APA
Zheng, K., Du, F., Sang, Y., Dong, K., Xiao, K., Zhang, R. ... Li, L. (2025). A FANCD2 gene mutation case analysis providing potential insights into the molecular mechanisms of gastric adenocarcinoma: A case report. Oncology Letters, 30, 422. https://doi.org/10.3892/ol.2025.15168
MLA
Zheng, K., Du, F., Sang, Y., Dong, K., Xiao, K., Zhang, R., Jing, C., Shang, L., Li, L."A FANCD2 gene mutation case analysis providing potential insights into the molecular mechanisms of gastric adenocarcinoma: A case report". Oncology Letters 30.3 (2025): 422.
Chicago
Zheng, K., Du, F., Sang, Y., Dong, K., Xiao, K., Zhang, R., Jing, C., Shang, L., Li, L."A FANCD2 gene mutation case analysis providing potential insights into the molecular mechanisms of gastric adenocarcinoma: A case report". Oncology Letters 30, no. 3 (2025): 422. https://doi.org/10.3892/ol.2025.15168
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