Top

Published in:

Open Access 01-12-2017 | Commentary

Genetic instability and increased mutational load: which diagnostic tool best direct patients with cancer to immunotherapy?

Authors: Giuseppe Palmieri, Maria Colombino, Antonio Cossu, Antonio Marchetti, Gerardo Botti, Paolo A. Ascierto

Published in: Journal of Translational Medicine | Issue 1/2017

Abstract

The occurrence of high rates of somatic mutations in cancer is believed to correspond to increased frequency of neo-epitope formation and tumor immunogenicity. Thus, classification of patients with cancer according to degree a somatic hyper-mutational status could be proposed as a predictive biomarker of responsiveness to immunotherapy with immune checkpoint inhibitors. Here, we discuss the suitable and reliable tests easily adoptable in clinical practice to assess somatic mutational status in patients with advanced cancer.

Snyder A, Makarov V, Merghoub T, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med. 2014;371:2189–99.CrossRefPubMedPubMedCentral

Rizvi NA, Hellmann MD, Snyder A, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348:124–8.CrossRefPubMedPubMedCentral

Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372:2509–20.CrossRefPubMedPubMedCentral

Van Allen EM, Miao D, Schilling B, et al. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science. 2015;350:207–11.CrossRefPubMedPubMedCentral

McGranahan N, Furness AJS, Rosenthal R, et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science. 2016;351:1463–9.CrossRefPubMedPubMedCentral

Hugo W, Zaretsky JM, Sun L, et al. Genomic and transcriptomic features of response to anti-PD-1 therapy in metastatic melanoma. Cell. 2016;165:35–44.CrossRefPubMed

Zaretsky JM, Garcia-Diaz A, Shin DS, et al. Mutations associated with acquired resistance to PD-1 blockade in melanoma. N Engl J Med. 2016;375:819–29.CrossRefPubMed

Lengauer C, Kinzier KW, Volgestein B. Genetic instabilities in human cancers. Nature. 1998;396:643–9.CrossRefPubMed

Sturzeneker R, Bevilacqua RA, Haddad LA, Simpson AJ, Pena SD. Microsatellite instability in tumors as a model to study the process of microsatellite mutations. Hum Mol Genet. 2000;9:347–52.CrossRefPubMed

10.

Richman S. Deficient mismatch repair: read all about it. Int J Oncol. 2015;47:1189–202.PubMedPubMedCentral

11.

Lee V, Murphy A, Le DT, Diaz LA Jr. Mismatch repair deficiency and response to immune checkpoint blockade. Oncologist. 2016;21:1200–11.CrossRefPubMed

12.

Graff JN, Alumkal JJ, Drake CG, et al. Early evidence of anti-PD-1 activity in enzalutamide-resistant prostate cancer. Oncotarget. 2016;33:52810–7.

13.

Jin Z, Yoon HH. The promise of PD-1 inhibitors in gastro-esophageal cancers: microsatellite instability vs. PD-L1. J Gastrointest Oncol. 2016;7:771–88.CrossRefPubMedPubMedCentral

14.

Le DT, Uram JN, Wang H, et al. PD-1 blockade in mismatch repair deficient non-colorectal gastrointestinal cancers. J Clin Oncol. 2016;34 (abstr):195.

15.

Sehdev A, Cramer HM, Ibrahim AA, Younger AE, O’Neil BH. Pathological complete response with anti-PD-1 therapy in a patient with microsatellite instable high, BRAF mutant metastatic colon cancer: a case report and review of literature. Discov Med. 2016;21:341–7.PubMed

16.

Kawakami H, Zaanan A, Sinicrope FA. MSI testing and its role in the management of colorectal cancer. Curr Treat Options Oncol. 2015;16:30.CrossRefPubMedPubMedCentral

17.

Chaves P, Cruz C, Lage P, et al. Immunohistochemical detection of mismatch repair gene proteins as a useful tool for the identification of colorectal carcinoma with the mutator phenotype. J Pathol. 2000;191:355–60.CrossRefPubMed

18.

Sameer AS, Nissar S, Fatima K. Mismatch repair pathway: molecules, functions, and role in colorectal carcinogenesis. Eur J Cancer Prev. 2014;23:246–57.CrossRefPubMed

19.

Goodfellow PJ, Billingsley CC, Lankes HA, et al. Combined microsatellite instability, MLH1 methylation analysis, and immunohistochemistry for Lynch Syndrome screening in endometrial cancers from GOG210: an NRG Oncology and Gynecologic Oncology Group Study. J Clin Oncol. 2015;33:4301–8.CrossRefPubMedPubMedCentral

20.

Baldinu P, Cossu A, Manca A, et al. Microsatellite instability and mutation analysis of candidate genes in unselected Sardinian patients with endometrial cancer. Cancer. 2002;94:3157–68.CrossRefPubMed

21.

Colombino M, Cossu A, Manca A, et al. Prevalence and prognostic role of microsatellite instability in patients with rectal carcinoma. Ann Oncol. 2002;13:1447–53.CrossRefPubMed

22.

Colombino M, Cossu A, Arba A, et al. Microsatellite instability and mutation analysis among Southern Italian patients with colorectal carcinoma: detection of different alterations accounting for MLH1 and MSH2 inactivation in familial cases. Ann Oncol. 2003;14:1530–6.CrossRefPubMed

23.

Strazzullo M, Cossu A, Baldinu P, et al. High-resolution methylation analysis of hMLH1 promoter in sporadic endometrial and colorectal carcinomas. Cancer. 2003;98:1540–6.CrossRefPubMed

24.

Colombino M, Cossu A, Budroni M, et al. Identification of predictive factors for the occurrence of predisposing MLH1 and MSH2 germline mutations among Sardinian patients with colorectal carcinoma. Eur J Cancer. 2005;41:1058–64.CrossRefPubMed

25.

Leite M, Corso G, Sousa S, et al. MSI phenotype and MMR alterations in familial and sporadic gastric cancer. Int J Cancer. 2011;128:1606–13.CrossRefPubMed

26.

Yamamoto H, Imai K. Microsatellite instability: an update. Arch Toxicol. 2015;89:899–921.CrossRefPubMed

27.

Shia J. Immunohistochemistry versus microsatellite instability testing for screening colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome. Part I. The utility of immunohistochemistry. J Mol Diagn. 2008;10:293–300.CrossRefPubMedPubMedCentral

28.

Umar A, Boland CR, Terdiman JP, et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004;96:261–8.CrossRefPubMedPubMedCentral

Title: Genetic instability and increased mutational load: which diagnostic tool best direct patients with cancer to immunotherapy?
Authors: Giuseppe Palmieri
Maria Colombino
Antonio Cossu
Antonio Marchetti
Gerardo Botti
Paolo A. Ascierto
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Journal of Translational Medicine / Issue 1/2017
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/s12967-017-1119-6

ACC 2024 Congress Coverage

Heart Failure Video

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Genetic instability and increased mutational load: which diagnostic tool best direct patients with cancer to immunotherapy?

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2017

Transcriptomic profiling and quantitative high-throughput (qHTS) drug screening of CDH1 deficient hereditary diffuse gastric cancer (HDGC) cells identify treatment leads for familial gastric cancer

On the brink of extinction: the future of translational physician-scientists in the United States

Association of osteopontin with specific prognostic factors and survival in adjuvant breast cancer trials of the Hellenic Cooperative Oncology Group

Erratum to: The progressive fragmentation of the KIT/PDGFRA wild-type (WT) gastrointestinal stromal tumors (GIST)

Microwave ablation combined with OK-432 induces Th1-type response and specific antitumor immunity in a murine model of breast cancer

Antibiotics-induced depletion of mice microbiota induces changes in host serotonin biosynthesis and intestinal motility

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page