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
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
June-2022 Volume 49 Issue 6

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
June-2022 Volume 49 Issue 6

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

Significance of rare variants in genes involved in the pathogenesis of Lynch syndrome

  • Authors:
    • Raffaella Liccardo
    • Matilde Lambiase
    • Antonio Nolano
    • Marina De Rosa
    • Paola Izzo
    • Francesca Duraturo
  • View Affiliations / Copyright

    Affiliations: Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, I‑80131 Napoli, Italy
    Copyright: © Liccardo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 81
    |
    Published online on: April 26, 2022
       https://doi.org/10.3892/ijmm.2022.5137
  • 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 molecular characterization of patients with Lynch syndrome (LS) involves germline testing to detect a deleterious mutation in one of the genes of the mismatch repair (MMR) pathway. To date, however, a large proportion of patients with a clinical suspicion of LS who undergo genetic testing do not show a germline pathogenetic variant in these genes. Germline DNA from 73 patients with a clinical suspicion of LS was examined with next‑generation sequencing methods, using a multigene custom panel designed and standardized by our research group, that targets a set of 15 genes. Deleterious variants were identified in 5.6% of index cases, while unclassified variants were identified in 80.3% of probands. To evaluate the pathogenicity of these uncertain variants, the American College of Medical Genetics and Genomics criteria was used, also considering wherever possible the microsatellite instability (MSI) status detected on tumor tissues as pathogenic criterion. In this manner, 8 of these uncertain significance variants were classified as likely pathogenic variants. Notably, some of these likely pathogenetic variants were also identified in the MLH3 gene that is a gene not routinely analyzed for cases with a clinical suspicion of LS. The present study highlighted the importance of verifying the pathogenicity of the numerous variants of unknown significance identified in patients for whom heredity is already clinically confirmed suggesting the importance of considering the MSI‑H status on the tumor of patients carrying an uncertain variant to evaluate its pathogenicity. Moreover, the present study also suggested analyzing other MMR genes, such as MLH3, in panels used for the molecular screening of LS.
View Figures

Figure 1

Figure 2

View References

1 

Jasperson KW, Tuohy TM, Neklason DW and Burt RW: Hereditary and familial colon cancer. Gastroenterology. 138:2044–2058. 2010. View Article : Google Scholar : PubMed/NCBI

2 

Kohlmann W: Lynch syndrome and breast cancer risk: Weighing the data. JCO Precis Oncol. Feb 26–2020.Epub ahead of print. View Article : Google Scholar

3 

Cerretelli G, Ager A, Arends MJ and Frayling IM: Molecular pathology of lynch syndrome. J Pathol. 250:518–531. 2020. View Article : Google Scholar : PubMed/NCBI

4 

Dodaro C, Grifasi C, Florio J, Santangelo ML, Duraturo F, De Rosa M, Izzo P and Renda A: The role of mutation analysis of the APC gene in the management of FAP patients. A controversial issue. Ann Ital Chir. 87:321–325. 2016.PubMed/NCBI

5 

Duraturo F, Liccardo R, De Rosa M and Izzo P: Genetics, diagnosis and treatment of lynch syndrome: Old lessons and current challenges. Oncol Lett. 17:3048–3054. 2019.

6 

Duraturo F, Liccardo R, Cavallo A, De Rosa M, Rossi GB and Izzo P: Multivariate analysis as a method for evaluating the pathogenicity of novel genetic MLH1 variants in patients with colorectal cancer and microsatellite instability. Int J Mol Med. 36:511–517. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Liccardo R, De Rosa M, Rossi GB, Carlomagno N, Izzo P and Duraturo F: Incomplete segregation of MSH6 frameshift variants with phenotype of lynch syndrome. Int J Mol Sci. 18:9992017. View Article : Google Scholar :

8 

Liccardo R, De Rosa M, Izzo P and Duraturo F: Novel MSH2 splice-site mutation in a young patient with lynch syndrome. Mol Med Rep. 17:6942–6946. 2018.

9 

Liccardo R, Della Ragione C, Mitilini N, De Rosa M, Izzo P and Duraturo F: Novel variants of unknown significance in the PMS2 gene identified in patients with hereditary colon cancer. Cancer. Manag Res. 18:6719–6725. 2019.

10 

Liccardo R, De Rosa M, Izzo P and Duraturo F: Novel implications in molecular diagnosis of lynch syndrome. Gastroenterol Res Pract. 2017:25950982017. View Article : Google Scholar : PubMed/NCBI

11 

Giardiello FM, Allen JI, Axilbund JE, Boland CR, Burke CA, Burt RW, Church JM, Dominitz JA, Johnson DA, Kaltenbach T, et al: Guidelines on genetic evaluation and management of lynch syndrome: A consensus statement by the US multi-society task force on colorectal cancer. Gastroenterology. 147:502–526. 2014. View Article : Google Scholar

12 

Duraturo F, Cavallo A, Liccardo R, Cudia B, De Rosa M, Diana G and Izzo P: Contribution of large genomic rearrangements in italian lynch syndrome patients: Characterization of a novel Alu-mediated deletion. Biomed Res Int. 2013:2198972013. View Article : Google Scholar : PubMed/NCBI

13 

Tognetto A, Pastorino R, Castorina S, Condorelli DF, DeCensi A, De Vito C, Magnano A, Scaldaferri F, Villari P, Genuardi M and Boccia S: The current practice of lynch syndrome diagnosis and management in Italy: A qualitative assessment. Public Health Genomics. 22:189–207. 2019. View Article : Google Scholar : PubMed/NCBI

14 

Lynch PM: The hMSH2 and hMLH1 genes in hereditary nonpolyposis colorectal cancer. Surg Oncol Clin N Am. 18:611–624. 2009. View Article : Google Scholar

15 

Hendriks YM, Wagner A, Morreau H, Menko F, Stormorken A, Quehenberger F, Sandkuijl L, Møller P, Genuardi M, Van Houwelingen H, et al: Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: Impact on counseling and surveillance. Gastroenterology. 127:17–25. 2004. View Article : Google Scholar : PubMed/NCBI

16 

Senter L, Clendenning M, Sotamaa K, Hampel H, Green J, Potter JD, Lindblom A, Lagerstedt K, Thibodeau SN, Lindor NM, et al: The clinical phenotype of lynch syndrome due to germ-line PMS2 mutations. Gastroenterology. 135:419–428. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Wu Y, Berends MJ, Sijmons RH, Mensink RG, Verlind E, Kooi KA, van der Sluis T, Kempinga C, van dDer Zee AG, Hollema H, et al: A role for MLH3 in hereditary nonpolyposis colorectal cancer. Nat Genet. 29:137–138. 2001. View Article : Google Scholar

18 

Moreira L, Balaguer F, Lindor N, de la Chapelle A, Hampel H, Aaltonen LA, Hopper JL, Le Marchand L, Gallinger S, Newcomb PA, et al: Identification of lynch syndrome among patients with colorectal cancer. JAMA. 17:1555–1565. 2012. View Article : Google Scholar

19 

Gupta S, Provenzale D, Llor X, Halverson AL, Grady W, Chung DC, Haraldsdottir S, Markowitz AJ, Slavin TP Jr, Hampel H, et al: NCCN guidelines insights: Genetic/familial high-risk assessment: Colorectal, version 2. 2019.J Natl Compr Canc Netw. 17:1032–1041. 2019. View Article : Google Scholar : PubMed/NCBI

20 

Vasen HF, Mecklin JP, Khan PM and Lynch HT: The International collaborative group on hereditary non-polyposis colorectal cancer (ICG-HNPCC). Dis Colon Rectum. 34:424–425. 1991. View Article : Google Scholar : PubMed/NCBI

21 

Vasen HF, Watson P, Mecklin JP and Lynch HT: New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) Proposed By the International Collaborative Group on HNPCC. Gastroenterology. 116:1453–1456. 1999. View Article : Google Scholar

22 

Gonzaga-Jauregui C, Lupski JR and Gibbs RA: Human genome sequencing in health and disease. Annu Rev Med. 63:35–61. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Turano M, Costabile V, Cerasuolo A, Duraturo F, Liccardo R, Delrio P, Pace U, Rega D, Dodaro CA, Milone M, et al: Characterisation of mesenchymal colon tumour-derived cells in tumourspheres as a model for colorectal cancer progression. Int J Oncol. 53:2379–2396. 2018.

24 

Fecteau H, Vogel KJ, Hanson K and Morrill-Cornelius S: The evolution of cancer risk assessment in the era of next generation sequencing. J Genet Couns. 23:633–639. 2014. View Article : Google Scholar : PubMed/NCBI

25 

Mardis ER: A decade's perspective on DNA sequencing technology. Nature. 470:198–203. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Lin EI, Tseng LH, Gocke CD, Reil S, Le DT, Azad NS and Eshleman JR: Mutational profiling of colorectal cancers with microsatellite instability. Oncotarget. 6:42334–42344. 2015. View Article : Google Scholar

27 

Kim JC, Choi JS, Roh SA, Cho DH, Kim TW and Kim YS: Promoter methylation of specific genes is associated with the phenotype and progression of colorectal adenocarcinomas. Ann Surg Oncol. 17:1767–1776. 2010. View Article : Google Scholar : PubMed/NCBI

28 

Liu C, Wang QS and Wang YJ: The CHEK2 I157T variant and colorectal cancer susceptibility: A systematic review and meta-analysis. Asian Pac J Cancer Prev. 13:2051–2055. 2012. View Article : Google Scholar

29 

Han P, Liu G, Lu X, Cao M, Yan Y, Zou J, Li X and Wang G: CDH1 rs9929218 Variant at 16q22.1 contributes to colorectal cancer susceptibility. Oncotarget. 26:47278–47286. 2016. View Article : Google Scholar

30 

Shenoy S: CDH1 (E-Cadherin) mutation and gastric cancer: Genetics, molecular mechanisms and guidelines for management. Cancer Manag Res. 13:10477–10486. 2019. View Article : Google Scholar

31 

Elzagheid A, Buhmeida A, Laato M, El-Faitori O, Syrjänen K, Collan Y and Pyrhönen S: Loss of E-cadherin expression predicts disease recurrence and shorter survival in colorectal carcinoma. APMIS. 120:539–548. 2012. View Article : Google Scholar : PubMed/NCBI

32 

Berndt SI, Platz EA, Fallin MD, Thuita LW, Hoffman SC and Helzlsouer KJ: Mismatch repair polymorphisms and the risk of colorectal cancer. Int J Cancer. 120:1548–1554. 2007. View Article : Google Scholar : PubMed/NCBI

33 

Orimo H, Nakajima E, Yamamoto M, Ikejima M, Emi M and Shimada T: Association between single nucleotide polymorphisms in the hMSH3 gene and sporadic colon cancer with microsatellite instability. J Hum Genet. 45:228–230. 2000. View Article : Google Scholar

34 

Jafary F, Salehi M, Sedghi M, Nouri N, Jafary F, Sadeghi F, Motamedi S and Talebi M: Association between mismatch repair gene MSH3 Codons 1036 and 222 polymorphisms and sporadic prostate cancer in the Iranian population. Asian Pac J Cancer Prev. 13:6055–6057. 2012. View Article : Google Scholar : PubMed/NCBI

35 

Duraturo F, Liccardo R, Cavallo A, De Rosa M, Grosso M and Izzo P: Association of low-risk MSH3 and MSH2 variant alleles with lynch syndrome: Probability of synergistic effects. Int J Cancer. 129:1643–1650. 2011. View Article : Google Scholar

36 

Adam R, Spier I, Zhao B, Kloth M, Marquez J, Hinrichsen I, Kirfel J, Tafazzoli A, Horpaopan S, Uhlhaas S, et al: Exome sequencing identifies biallelic MSH3 germline mutations as a recessive subtype of colorectal adenomatous polyposis. Am J Hum Genet. 99:337–351. 2016. View Article : Google Scholar : PubMed/NCBI

37 

Olkinuora A, Nieminen TT, Mårtensson E, Rohlin A, Ristimäki A, Koskenvuo L, Lepistö A; Swedish Extended Genetic Analysis of Colorectal Neoplasia (SWEN) Study Group; Gebre-Medhin S, Nordling M and Peltomäki P: Biallelic germline nonsense variant of MLH3 underlies polyposis predisposition. Genet Med. 21:1868–1873. 2019. View Article : Google Scholar

38 

Duraturo F, Liccardo R and Izzo P: Coexistence of MLH3 germline variants in colon cancer patients belonging to families with lynch syndrome-associated brain tumors. J Neurooncol. 129:577–578. 2016. View Article : Google Scholar : PubMed/NCBI

39 

Titze S, Peters H, Währisch S, Harder T, Guse K, Buske A, Tinschert S and Harder A: Differential MSH2 promoter methylation in blood cells of Neurofibromatosis type 1 (NF1) patients. Eur J Hum Genet. 18:81–87. 2010. View Article : Google Scholar :

40 

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 :

41 

Desmet FO, Hamroun D, Lalande M, Collod-Béroud G, Claustres M and Béroud C: Human splicing finder: An online bio-informatics tool to predict splicing signals. Nucleic Acids Res. 37:e672009. View Article : Google Scholar

42 

Ramensky V, Bork P and Sunyaev S: Human non-synonymous SNPs: Server and survey. Nucleic Acids Res. 30:3894–3900. 2002. View Article : Google Scholar : PubMed/NCBI

43 

Rost B, Yachdav G and Liu J: The predictprotein server. Nucleic Acids Res. 32:W321–W326. 2004. View Article : Google Scholar :

44 

Schwarz JM, Rödelsperger C, Schuelke M and Seelow D: Mutationtaster evaluates disease-causing potential of sequence alterations. Nat Methods. 7:575–576. 2010. View Article : Google Scholar

45 

Choi Y, Sims GE, Murphy S, Miller JR and Chan AP: Predicting the functional effect of amino acid substitutions and indels. PLoS One. 7:e466882012. View Article : Google Scholar : PubMed/NCBI

46 

Zhunussova G, Afonin G, Abdikerim S, Jumanov A, Perfilyeva A, Kaidarova D and Djansugurova L: Mutation spectrum of cancer-associated genes in patients with early onset of colorectal cancer. Front Oncol. 9:6732019. View Article : Google Scholar :

47 

Liccardo R, Nolano A, Lambiase M, Della Ragione C, De Rosa M, Izzo P and Duraturo F: MSH2 overexpression due to an unclassified variant in 3-Untranslated region in a patient with colon cancer. Biomedicines. 8:1672020. View Article : Google Scholar

48 

Arora S, Huwe PJ, Sikder R, Shah M, Browne AJ, Lesh R, Nicolas E, Deshpande S, Hall MJ, Dunbrack RL Jr and Golemis EA: Functional analysis of rare variants in mismatch repair proteins augments results from computation-based predictive methods. Cancer Biol Ther. 18:519–533. 2017. View Article : Google Scholar :

49 

Jia X, Burugula BB, Chen V, Lemons RM, Jayakody S, Maksutova M and Kitzman JO: Massively parallel functional testing of MSH2 missense variants conferring lynch syndrome risk. Am J Hum Genet. 108:163–175. 2021. View Article : Google Scholar

50 

Hegan DC, Narayanan L, Jirik FR, Edelmann W, Liskay RM and Glazer PM: Differing patterns of genetic instability in mice deficient in the mismatch repair genes Pms2, Mlh1, Msh2, Msh3 and Msh6. Carcinogenesis. 27:2402–5408. 2006. View Article : Google Scholar : PubMed/NCBI

51 

Loukola A, Vilkki S, Singh J, Launonen V and Aaltonen LA: Germline and somatic mutation analysis of MLH3 in MSI-positive colorectal cancer. Am J Pathol. 157:347–352. 2000. View Article : Google Scholar

52 

Turano M, Delrio P, Rega D, Cammarota F, Polverino A, Duraturo F, Izzo P and De Rosa M: Promising colorectal cancer biomarkers for precision prevention and therapy. Cancers (Basel). 11:19322019. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Liccardo R, Lambiase M, Nolano A, De Rosa M, Izzo P and Duraturo F: Significance of rare variants in genes involved in the pathogenesis of Lynch syndrome. Int J Mol Med 49: 81, 2022.
APA
Liccardo, R., Lambiase, M., Nolano, A., De Rosa, M., Izzo, P., & Duraturo, F. (2022). Significance of rare variants in genes involved in the pathogenesis of Lynch syndrome. International Journal of Molecular Medicine, 49, 81. https://doi.org/10.3892/ijmm.2022.5137
MLA
Liccardo, R., Lambiase, M., Nolano, A., De Rosa, M., Izzo, P., Duraturo, F."Significance of rare variants in genes involved in the pathogenesis of Lynch syndrome". International Journal of Molecular Medicine 49.6 (2022): 81.
Chicago
Liccardo, R., Lambiase, M., Nolano, A., De Rosa, M., Izzo, P., Duraturo, F."Significance of rare variants in genes involved in the pathogenesis of Lynch syndrome". International Journal of Molecular Medicine 49, no. 6 (2022): 81. https://doi.org/10.3892/ijmm.2022.5137
Copy and paste a formatted citation
x
Spandidos Publications style
Liccardo R, Lambiase M, Nolano A, De Rosa M, Izzo P and Duraturo F: Significance of rare variants in genes involved in the pathogenesis of Lynch syndrome. Int J Mol Med 49: 81, 2022.
APA
Liccardo, R., Lambiase, M., Nolano, A., De Rosa, M., Izzo, P., & Duraturo, F. (2022). Significance of rare variants in genes involved in the pathogenesis of Lynch syndrome. International Journal of Molecular Medicine, 49, 81. https://doi.org/10.3892/ijmm.2022.5137
MLA
Liccardo, R., Lambiase, M., Nolano, A., De Rosa, M., Izzo, P., Duraturo, F."Significance of rare variants in genes involved in the pathogenesis of Lynch syndrome". International Journal of Molecular Medicine 49.6 (2022): 81.
Chicago
Liccardo, R., Lambiase, M., Nolano, A., De Rosa, M., Izzo, P., Duraturo, F."Significance of rare variants in genes involved in the pathogenesis of Lynch syndrome". International Journal of Molecular Medicine 49, no. 6 (2022): 81. https://doi.org/10.3892/ijmm.2022.5137
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