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
January-2025 Volume 29 Issue 1

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
January-2025 Volume 29 Issue 1

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

  • Supplementary Files
    • Supplementary_Data1.pdf
    • Supplementary_Data2.pdf
Article

Genetic evaluation of patients with multiple primary cancers

  • Authors:
    • Maria Valeria Freire
    • Romain Thissen
    • Marie Martin
    • Corinne Fasquelle
    • Laura Helou
    • Keith Durkin
    • Maria Artesi
    • Aimé Lumaka
    • Natacha Leroi
    • Karin Segers
    • Michelle Deberg
    • Jean-Stéphane Gatot
    • Lionel Habran
    • Leonor Palmeira
    • Claire Josse
    • Vincent Bours
  • View Affiliations / Copyright

    Affiliations: Department of Human Genetics, GIGA Research Center‑University of Liège and CHU Liège, 4000 Liège, Belgium, Department of Human Genetics, CHU Liège, 4000 Liège, Belgium, Department of Pathology, CHU Liège, 4000 Liège, Belgium, Department of Medical Oncology, GIGA Research Center‑University of Liège and CHU Liège, 4000 Liège, Belgium
  • Article Number: 4
    |
    Published online on: October 15, 2024
       https://doi.org/10.3892/ol.2024.14750
  • 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

Regarding inherited cancer predisposition, single gene carriers of pathogenic variants (PVs) have been extensively reported on in the literature, whereas the oligogenic coinheritance of heterozygous PVs in cancer‑related genes is a poorly studied event. Currently, due to the increased number of cancer survivors, the probability of patients presenting with multiple primary cancers (MPCs) is higher. The present study included patients with MPCs aged ≤45 years without known PVs in common cancer predisposition genes. This study used whole exome sequencing (WES) of germline and tumoral DNA, chromosomal microarray analysis (CMA) of germline DNA (patients 1‑7, 9 and 10), and a karyotype test of patient 8 to detect variants associated with the disease. The 10 patients included in the study presented a mean of 3 cancers per patient. CMA showed two microduplications and one microdeletion, while WES of the germline DNA identified 1‑3 single nucleotide variants of potential interest to the disease in each patient and two additional copy number variants. Most of the identified variants were classified as variants of uncertain significance. The mapping of the germline variants into their pathways showed a possible additive effect of these as the cause of the cancer. A total of 12 somatic samples from 5 patients were available for sequencing. All of the germline variants were also present in the somatic samples, while no second hits were identified in the same genes. The sequencing of patients with early cancers, family history and multiple tumors is already a standard of care. However, growing evidence has suggested that the assessment of patients should not stop at the identification of one PV in a cancer predisposition gene.
View Figures
View References

1 

Dickie L, Johnson CH, Adams S and Serban N: Solid tumor rules. Effective with Cases Diagnosed 1/1/2018 and Forward. National Cancer; Rockville, MD: 2021, https://seer.cancer.gov/tools/solidtumor/STM.pdfMarch 9–2023

2 

Report WG: International rules for multiple primary cancers (ICD-0 third edition). Eur J Cancer Prev. 14:307–308. 2005. View Article : Google Scholar

3 

American Cancer Society, . Cancer Facts & Figures 2009. American Cancer Society; Atlanta, GA: 2019, https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2009.htmlApril 6–2023

4 

Cybulski C, Nazarali S and Narod SA: Multiple primary cancers as a guide to heritability. Int J Cancer. 135:1756–1763. 2014. View Article : Google Scholar

5 

Chan GHJ, Ong PY, Low JJH, Kong HL, Ow SGW, Tan DSP, Lim YW, Lim SE and Lee SC: Clinical genetic testing outcome with multi-gene panel in Asian patients with multiple primary cancers. Oncotarget. 9:30649–30660. 2018. View Article : Google Scholar

6 

Harvengt J, Lumaka A, Fasquelle C, Caberg JH, Mastouri M, Janssen A, Palmeira L and Bours V: HIDEA syndrome: A new case report highlighting similarities with ROHHAD syndrome. Front Genet. 14:11377672023. View Article : Google Scholar

7 

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, et al: Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology. Genet Med. 17:405–424. 2015. View Article : Google Scholar

8 

Backenroth D, Homsy J, Murillo LR, Glessner J, Lin E, Brueckner M, Lifton R, Goldmuntz E, Chung WK and Shen Y: CANOES: Detecting rare copy number variants from whole exome sequencing data. Nucleic Acids Res. 42:e972014. View Article : Google Scholar

9 

Riggs ER, Andersen EF, Cherry AM, Kantarci S, Kearney H, Patel A, Raca G, Ritter DI, South ST, Thorland EC, et al: Technical standards for the interpretation and reporting of constitutional copy number variants: A joint consensus recommendation of the American college of medical genetics and genomics (ACMG) and the clinical genome resource (ClinGen). Genet Med. 22:245–257. 2020. View Article : Google Scholar

10 

Li MM, Datto M, Duncavage EJ, Kulkarni S, Lindeman NI, Roy S, Tsimberidou AM, Vnencak-Jones CL, Wolff DJ, Younes A and Nikiforova MN: Standards and guidelines for the interpretation and reporting of sequence variants in cancer. J Mol Diagn. 19:4–23. 2017. View Article : Google Scholar

11 

Blokzijl F, Janssen R, van Boxtel R and Cuppen E: MutationalPatterns: Comprehensive genome-wide analysis of mutational processes. Genome Med. 10:332018. View Article : Google Scholar

12 

Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, Bignell GR, Bolli N, Borg A, Børresen-Dale AL, et al: Signatures of mutational processes in human cancer. Nature. 500:415–421. 2013. View Article : Google Scholar

13 

Nielsen M, Joerink-van de Beld MC, Jones N, Vogt S, Tops CM, Vasen HFA, Sampson JR, Aretz S and Hes FJ: Analysis of MUTYH genotypes and colorectal phenotypes in patients with MUTYH-associated polyposis. Gastroenterology. 136:471–476. 2009. View Article : Google Scholar

14 

Barreiro RAS, Sabbaga J, Rossi BM, Achatz MIW, Bettoni F, Camargo AA, Asprino PF and Galante PAF: Monoallelic deleterious MUTYH germline variants as a driver for tumorigenesis. J Pathol. 256:214–222. 2022. View Article : Google Scholar

15 

Abou Tayoun AN, Pesaran T, DiStefano MT, Oza A, Rehm HL, Biesecker LG and Harrison SM; ClinGen Sequence Variant Interpretation Working Group (ClinGen SVI), : Recommendations for interpreting the loss of function PVS1 ACMG/AMP variant criterion. Hum Mutat. 39:1517–1524. 2018. View Article : Google Scholar

16 

Whitworth J, Smith PS, Martin JE, West H, Luchetti A, Rodger F, Clark G, Carss K, Stephens J, Stirrups K, et al: Comprehensive cancer-predisposition gene testing in an adult multiple primary tumor series shows a broad range of deleterious variants and atypical tumor phenotypes. Am J Hum Genet. 103:3–18. 2018. View Article : Google Scholar

17 

Liu YL, Cadoo KA, Mukherjee S, Khurram A, Tkachuk K, Kemel Y, Maio A, Belhadj S, Carlo MI, Latham A, et al: Multiple primary cancers in patients undergoing tumor-normal sequencing define novel associations. Cancer Epidemiol Biomarkers Prev. 31:362–371. 2022. View Article : Google Scholar

18 

McGuigan A, Whitworth J, Andreou A, Hearn T, Tischkowitz M and Maher ER: Multilocus inherited neoplasia allele syndrome (MINAS): An update. Eur J Hum Genet. 30:265–270. 2022. View Article : Google Scholar

19 

Aston CE, Ralph DA, Lalo DP, Manjeshwar S, Gramling BA, DeFreese DC, West AD, Branam DE, Thompson LF, Craft MA, et al: Oligogenic combinations associated with breast cancer risk in women under 53 years of age. Hum Genet. 116:208–221. 2005. View Article : Google Scholar

20 

Renieri A, Mencarelli MA, Cetta F, Baldassarri M, Mari F, Furini S, Piu P, Ariani F, Dragani TA and Frullanti E: Oligogenic germline mutations identified in early non-smokers lung adenocarcinoma patients. Lung Cancer. 85:168–1674. 2014. View Article : Google Scholar

21 

Weischer M, Heerfordt IM, Bojesen SE, Eigentler T, Garbe C, Röcken M, Hölmich LR, Schmidt H, Klyver H, Bastholt L and Nordestgaard BG: CHEK2*1100delC and risk of malignant melanoma: Danish and German studies and meta-analysis. J Invest Dermatol. 132:299–303. 2012. View Article : Google Scholar

22 

AlDubayan SH, Pyle LC, Gamulin M, Kulis T, Moore ND, Taylor-Weiner A, Hamid AA, Reardon B, Wubbenhorst B, Godse R, et al: Association of inherited pathogenic variants in checkpoint kinase 2 (CHEK2) with susceptibility to testicular germ cell tumors. JAMA Oncol. 5:514–522. 2019. View Article : Google Scholar

23 

Stolarova L, Kleiblova P, Janatova M, Soukupova J, Zemankova P, Macurek L and Kleibl Z: CHEK2 germline variants in cancer predisposition: Stalemate rather than checkmate. Cells. 9:26752020. View Article : Google Scholar

24 

Xu J, Zheng SL, Komiya A, Mychaleckyj JC, Isaacs SD, Hu JJ, Sterling D, Lange EM, Hawkins GA, Turner A, et al: Germline mutations and sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk. Nat Genet. 32:321–325. 2002. View Article : Google Scholar

25 

Orloff M, Peterson C, He X, Ganapathi S, Heald B, Yang YR, Bebek G, Romigh T, Song JH, Wu W, et al: Germline mutations in MSR1, ASCC1, and CTHRC1 in patients with barrett esophagus and esophageal adenocarcinoma. JAMA. 306:410–419. 2011. View Article : Google Scholar

26 

Wen WX, Soo JS, Kwan PY, Hong E, Khang TF, Mariapun S, Lee CS, Hasan SN, Rajadurai P, Yip CH, et al: Germline APOBEC3B deletion is associated with breast cancer risk in an Asian multi-ethnic cohort and with immune cell presentation. Breast Cancer Res. 18:562016. View Article : Google Scholar

27 

Vega-Stromberg T: Chemotherapy-induced secondary malignancies. J Infus Nurs. 26:3532003. View Article : Google Scholar

28 

Freire Chadrina M, Martin M and Segers K: Sepulchre. Coinheritance of pathogenic variants in ATM and BRCA2 in families with multiple cancers: A case series (Internet). 2022.(cited 2023 Feb 23).

29 

Vietri MT, Caliendo G, D'Elia G, Resse M, Casamassimi A, Minucci PB, Dello Ioio C, Cioffi M and Molinari AM: Five Italian families with two mutations in BRCA genes. Genes (Basel). 11:14512020. View Article : Google Scholar

30 

Huang W, Bian J, Qian X, Shao L, Li H, Zhang L and Wang L: Case report: Coinheritance of germline mutations in APC and BRCA1 in colorectal cancer. Front Oncol. 11:6583892021. View Article : Google Scholar

31 

Borde J, Ernst C, Wappenschmidt B, Niederacher D, Weber-Lassalle K, Schmidt G, Hauke J, Quante AS, Weber-Lassalle N, Horváth J, et al: Performance of breast cancer polygenic risk scores in 760 female CHEK2 germline mutation carriers. J Natl Cancer Inst. 113:893–899. 2020. View Article : Google Scholar

32 

Potorac I, Laterre M, Malaise O, Nechifor V, Fasquelle C, Colleye O, Detrembleur N, Verdin H, Symoens S, De Baere E, et al: The role of MCM9 in the etiology of sertoli cell-only syndrome and premature ovarian insufficiency. J Clin Med. 12:9902023. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Freire MV, Thissen R, Martin M, Fasquelle C, Helou L, Durkin K, Artesi M, Lumaka A, Leroi N, Segers K, Segers K, et al: Genetic evaluation of patients with multiple primary cancers. Oncol Lett 29: 4, 2025.
APA
Freire, M.V., Thissen, R., Martin, M., Fasquelle, C., Helou, L., Durkin, K. ... Bours, V. (2025). Genetic evaluation of patients with multiple primary cancers. Oncology Letters, 29, 4. https://doi.org/10.3892/ol.2024.14750
MLA
Freire, M. V., Thissen, R., Martin, M., Fasquelle, C., Helou, L., Durkin, K., Artesi, M., Lumaka, A., Leroi, N., Segers, K., Deberg, M., Gatot, J., Habran, L., Palmeira, L., Josse, C., Bours, V."Genetic evaluation of patients with multiple primary cancers". Oncology Letters 29.1 (2025): 4.
Chicago
Freire, M. V., Thissen, R., Martin, M., Fasquelle, C., Helou, L., Durkin, K., Artesi, M., Lumaka, A., Leroi, N., Segers, K., Deberg, M., Gatot, J., Habran, L., Palmeira, L., Josse, C., Bours, V."Genetic evaluation of patients with multiple primary cancers". Oncology Letters 29, no. 1 (2025): 4. https://doi.org/10.3892/ol.2024.14750
Copy and paste a formatted citation
x
Spandidos Publications style
Freire MV, Thissen R, Martin M, Fasquelle C, Helou L, Durkin K, Artesi M, Lumaka A, Leroi N, Segers K, Segers K, et al: Genetic evaluation of patients with multiple primary cancers. Oncol Lett 29: 4, 2025.
APA
Freire, M.V., Thissen, R., Martin, M., Fasquelle, C., Helou, L., Durkin, K. ... Bours, V. (2025). Genetic evaluation of patients with multiple primary cancers. Oncology Letters, 29, 4. https://doi.org/10.3892/ol.2024.14750
MLA
Freire, M. V., Thissen, R., Martin, M., Fasquelle, C., Helou, L., Durkin, K., Artesi, M., Lumaka, A., Leroi, N., Segers, K., Deberg, M., Gatot, J., Habran, L., Palmeira, L., Josse, C., Bours, V."Genetic evaluation of patients with multiple primary cancers". Oncology Letters 29.1 (2025): 4.
Chicago
Freire, M. V., Thissen, R., Martin, M., Fasquelle, C., Helou, L., Durkin, K., Artesi, M., Lumaka, A., Leroi, N., Segers, K., Deberg, M., Gatot, J., Habran, L., Palmeira, L., Josse, C., Bours, V."Genetic evaluation of patients with multiple primary cancers". Oncology Letters 29, no. 1 (2025): 4. https://doi.org/10.3892/ol.2024.14750
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