DNA mismatch repair deficiency and hereditary syndromes in Latino patients with colorectal cancer

Ricker, Charité; Hanna, Diana L.; Peng, Cheng; Nguyen, Nathalie; Stern, Mariana C.; Schmit, Stephanie L.; Idos, Greg E.; Patel, Ravi; Tsai, Shau‐Wei; Ramirez, Veronica; Lin, Steve; Shamasunadara, Vinay; Barzi, Afsaneh; Lenz, Heinz‐Josef; Figueiredo, Jane C.

doi:10.1002/cncr.30790

Cited by 21 publications

(21 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The percentage of MMR gene mutations in the tumors was approximately 13% in Latino individuals, which is similar to estimates in non-Hispanic white individuals. Furthermore, approximately 61.9% of deficient MMR tumors were indeed attributable to germline MMR gene mutations by in-depth molecular analysis, and Latino patients with Lynch syndrome develop cancer at a younger age and have a higher percentage of rectal cancers and advanced disease, which is consistent with observations in other studies [ 40 ]. The incidence of Lynch syndrome among diagnosed CRC patients in Japan is 0.7%, which is slightly lower than that reported previously but within the same range (0.7–3.7%) as that in recent investigations [ 41 ].…”

Section: Lynch Syndromesupporting

confidence: 90%

Hereditary Nonpolyposis Colorectal Cancer and Cancer Syndromes: Recent Basic and Clinical Discoveries

Chen

Liu

2018

Journal of Oncology

View full text Add to dashboard Cite

Approximately one-third of individuals diagnosed with colorectal cancer have a family history of cancer, suggesting that CRCs may result from a heritable component. Despite the availability of current gene-identification techniques, only 5% of all CRCs emerge from well-identifiable inherited causes for predisposition, including polyposis and nonpolyposis syndromes. Hereditary nonpolyposis colorectal cancer represents a large proportion of cases, and robustly affected patients are at increased risk for early onset, synchronous, and metachronous colorectal malignancies and extracolonic malignancies. HNPCC encompasses several cancer syndromes, such as Lynch syndrome, Lynch-like syndrome, and familial colorectal cancer type X, which have remarkable clinical presentations and overlapping genetic profiles that make clinical diagnosis a challenging task. Therefore, distinguishing between the HNPCC disorders is crucial for physicians as an approach to tailor different recommendations for patients and their at-risk family members according to the risks for colonic and extracolonic cancer associated with each syndrome. Identification of these potential patients through epidemiological characteristics and new genetic testing can estimate the individual risk, which informs appropriate cancer screening, surveillance, and/or treatment strategies. In the past three years, many appealing and important advances have been made in our understanding of the relationship between HNPCC and CRC-associated syndromes. The knowledge from the genetic profile of cancer syndromes and unique genotype-phenotype profiles in the different syndromes has changed our cognition. Therefore, this review presents and discusses HNPCC and several common nonpolyposis syndromes with respect to molecular phenotype, histopathologic features, and clinical presentation.

show abstract

Section: Lynch Syndromesupporting

confidence: 90%

Hereditary Nonpolyposis Colorectal Cancer and Cancer Syndromes: Recent Basic and Clinical Discoveries

Chen

Liu

2018

Journal of Oncology

View full text Add to dashboard Cite

show abstract

“…In addition, the rates of cancer incidence and mortality are higher in Northern Mexico 18 . These and our study findings, in addition to lack of evidence to support that genetics plays an important role in the higher incidence of CRC in Hispanics [19][20][21] , suggest that the adoption of more Western lifestyles and associated complications are the main culprits for the higher incidence rates of CRC in border communities.…”

Section: Discussioncontrasting

confidence: 60%

Colorectal cancer in hispanics living near the U.S. - Mexico Border

Robles

Bashashati

Contreras

et al. 2020

RIC

View full text Add to dashboard Cite

Background: The incidence of colorectal cancer (CRC) in the US has declined. The decreasing trend is observed in non-Hispanic Whites, Blacks, and Hispanics. However, close analysis of the trends demonstrates that the decline among Hispanics is less than other races/ethnicities. We investigate the burden of CRC in Hispanics living near the U.S.-Mexico border, a subpopulation of Hispanics composed primarily of individuals of Mexican origin. Objectives: The objective of this study was to investigate and compare incidence rates of CRC in non-Hispanic Whites and Hispanics living in counties along the U.S.-Mexico border. Methods: Data from the National Institutes of Health National Cancer Institute and State Cancer Profiles were analyzed to obtain CRC incidence rates (per 100,000 population) for persons ≥ 50 years of age residing in counties along the U.S.-Mexico border by race (non-Hispanic White and Hispanic) and gender from 2011 to 2015. Results: Incidence rates of CRC in Hispanic men ≥ 50 years of age, living in counties along the U.S.-Mexico border, were higher than the national average for Hispanic men of similar age. In contrast, the incidence of CRC declined or remained stable in non-Hispanic Whites and women. Conclusions: Our study unveils a significant disparity in CRC incidence among Hispanics living near the U.S.-Mexico border, disproportionally affecting men ≥ 50 years of age. Socioeconomic and cultural/lifestyle factors are likely contributing to these disparities.

show abstract

“…Given the existence of immune-relevant FSP neoantigens that may be bound only by a certain type of HLA molecules, it is reasonable to assume that HLA genotype may be a modifier of cancer risk. This may also explain possible variations of Lynch syndrome penetrance or different rates of MMR deficiency previously suspected between distinct populations (60). Future studies on the natural course of Lynch syndrome should account for this factor.…”

Section: Discussionmentioning

confidence: 91%

The sharedneoantigen landscape of MSI cancers reflects immunoediting during tumor evolution

Ballhausen

Przybilla

Jendrusch

et al. 2019

Preprint

View full text Add to dashboard Cite

Glossary TermMeaning ELS Epitope likelihood score GELS General epitope likelihood score IRS Immune relevance score, based on the mutation frequency (ReFrame) and the GELS M1Reading frame resulting from the deletion of one nucleotide or insertions of two nucleotides M2Reading frame resulting from the deletions of two nucleotides or insertion of one nucleotide m1, m2, m3, etc.Minus one, two, three base pair deletions p1, p2, p3, etc.Plus one, two, three base pair insertions ReFrameREgression-based FRAMEshift quantification Abbreviations B2M Beta2-microglobulin cMS Coding microsatellites CRC Colorectal cancer MMR Mismatch repair EC Endometrium cancer FSP neoantigens Frameshift peptide neoantigens HLA Human leukocyte antigen ICB Immune checkpoint blockade MSI Microsatellite instability, microsatelliteunstable NGSNext generation sequencing Abstract:The immune system can recognize and attack cancer cells, especially those with a high load of mutation-induced neoantigens. Such neoantigens are particularly abundant in DNA mismatch repair (MMR)-deficient, microsatellite-unstable (MSI) cancers. MMR deficiency leads to insertion/deletion (indel) mutations at coding microsatellites (cMS) and to neoantigen-inducing translational frameshifts. The abundance of mutational neoantigens renders MSI cancers sensitive to immune checkpoint blockade. However, the neoantigen landscape of MMR-deficient cancers has not yet been systematically mapped. In the present study, we used a novel tool to monitor neoantigen-inducing indel mutations in MSI colorectal and endometrial cancer. Our results show that MSI cancers share several highly immunogenic neoantigens that result from specific, recurrent indel mutation events.Notably, the frequency of such indel mutations was negatively correlated to the predicted immunogenicity of the resulting neoantigens. These observations suggest continuous immunoediting of emerging MMR-deficient cells during tumor evolution. Main text:DNA MMR deficiency is a major mechanism causing genomic instability in human cancer. MMR-deficient cancers accumulate an exceptionally high number of somatic mutations. These mutations encompass certain types of single nucleotide alterations, but mostly insertion/deletion (indel) mutations at repetitive sequence stretches termed microsatellites (microsatellite instability, MSI) (1, 2). About 15% of colorectal cancers (CRC), up to 30% of endometrial cancers (EC) and multiple other tumors display the MSI phenotype (3). MSI tumors can develop sporadically or in the context of Lynch syndrome, the most common inherited cancer predisposition syndrome. Due to this very specific process of genomic instability, the pathogenesis of MSI cancers can be precisely dissected (4): Indel mutations affecting coding microsatellites (cMS), predominantly coding mononucleotide repeats, in genomic regions encoding tumor suppressor genes are considered major drivers of MSI tumorigenesis (5-7). Importantly, the same indels that inactivate tumor suppressor genes simultaneously cause translational frameshi...

show abstract

DNA mismatch repair deficiency and hereditary syndromes in Latino patients with colorectal cancer

Cited by 21 publications

References 48 publications

Hereditary Nonpolyposis Colorectal Cancer and Cancer Syndromes: Recent Basic and Clinical Discoveries

Hereditary Nonpolyposis Colorectal Cancer and Cancer Syndromes: Recent Basic and Clinical Discoveries

Colorectal cancer in hispanics living near the U.S. - Mexico Border

The sharedneoantigen landscape of MSI cancers reflects immunoediting during tumor evolution

Contact Info

Product

Resources

About