Recent Advances in Lynch Syndrome: Diagnosis, Treatment, and Cancer Prevention

2018 ◽  
pp. 101-109 ◽  
Author(s):  
Matthew B. Yurgelun ◽  
Heather Hampel
Keyword(s):  
Lynch Syndrome ◽  
Cancer Prevention ◽  
Checkpoint Inhibitors ◽  
Tremendous Progress ◽  
Cancer Prevention And Screening ◽  
Reduction Strategies ◽  
Neoplastic Process ◽  
Risk Reduction Strategies ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Identification of individuals with inherited predispositions to cancer, including Lynch syndrome, can help prevent cancer and cancer-related death by allowing for the uptake of specific cancer prevention and screening as well as the use of therapies directed toward the underlying neoplastic process for individuals with advanced cancer. In the 25 years since the discovery of microsatellite instability (MSI) and the first recognition of germline mismatch repair (MMR) gene variants as the etiologic basis of Lynch syndrome, there has been tremendous progress in the understanding of the spectrum of cancer risk associated with Lynch syndrome as well as in cancer prevention and risk-reduction strategies. The past few years, in particular, have brought transformative changes in the treatment of Lynch syndrome–associated cancers with immune checkpoint inhibitors. In parallel, advances in next-generation sequencing (NGS) technologies now allow rapid and scalable somatic and germline sequencing that promises to help identify Lynch syndrome in individuals who otherwise lack classic phenotypes. Last, real progress is being made to understand more sophisticated methods of precision cancer prevention, including chemotherapeutic prevention agents (e.g., aspirin) and strategies that leverage the immune system to facilitate primary cancer prevention in otherwise-healthy Lynch syndrome carriers.

scholarly journals Canine Genetics and Genomics

2021 ◽  
Author(s):  
Edo D’Agaro ◽  
Andrea Favaro ◽  
Davide Rosa
Keyword(s):  
Heart Disease ◽  
Next Generation Sequencing ◽  
Genomic Data ◽  
Behavioral Traits ◽  
Canine Genetics ◽  
Genome Wide ◽  
Tremendous Progress ◽  
Dog Breed ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

In the past fifteen years, tremendous progress has been made in dog genomics. Several genetic aspects of cancer, heart disease, hip dysplasia, vision and hearing problems in dogs have been investigated and studied in detail. Genome-wide associative studies have made it possible to identify several genes associated with diseases, morphological and behavioral traits. The dog genome contains an extraordinary amount of genetic variability that distinguishes the different dog breeds. As a consequence of the selective programs, applied using stringent breed standards, each dog breed represents, today, a population isolated from the others. The availability of modern next generation sequencing (NGS) techniques and the identification of millions of single functional mutations (SNPs) has enabled us to obtain new and unknown detailed genomic data of the different breeds.

Using next-generation sequencing (NGS) to identify causative mutations in Asian cancer (CA) patients with suspected Lynch syndrome.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 1540-1540
Author(s):  
Samuel Guan Wei Ow ◽  
Kar Tong Tan ◽  
Henry Yang ◽  
Hui-Ling Yap ◽  
Nur Sabrina Binte Sapari ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Lynch Syndrome ◽  
Next Generation ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

scholarly journals Use of Biomarkers in Individualization of Treatment

2020 ◽  
Vol 18 (7.5) ◽  
pp. 989-991
Author(s):  
Jennifer J.D. Morrissette
Keyword(s):  
Massively Parallel Sequencing ◽  
Checkpoint Inhibitors ◽  
Genetic Alterations ◽  
Massively Parallel ◽  
Disease Course ◽  
Patients With Cancer ◽  
Appropriate Treatment ◽  
Clinical Trial Enrollment ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Next-generation sequencing (NGS), also known as massively parallel sequencing (MPS), offers broad detection of genetic alterations that, in approximately one-third of patients with cancer, are “actionable,” meaning that they can be targeted by available therapeutics or the detection of the alteration can lead to a change in therapy. NGS is useful in the diagnosis of patients, determining their prognosis, appropriate treatment selection, and clinical trial enrollment. Many testing panels are available, each with different abilities to detect various mutation types. Clinicians not only have to decide which test to use, but which specimen to test, and when and how often to test. Aside from unique mutations, immunotherapy markers have become important for the use of checkpoint inhibitors, and their detection and interpretation can also be challenging. Efforts are underway to simplify and validate these assays. Meanwhile, clinicians should become educated about the benefit of, means of, and interpretation of genomic testing patients across the disease course.

Plasma next-generation sequencing (NGS) in advanced non-small cell lung cancer (aNSCLC) patients (pts) treated with immune checkpoint inhibitors (ICIs): Impact of STK11 and TP53 mutations on outcome.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3046-3046
Author(s):  
Alberto Pavan ◽  
Elisabetta Zulato ◽  
Lorenzo Calvetti ◽  
Alessandra Ferro ◽  
Giorgia Nardo ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Genetic Alterations ◽  
Predictive Markers ◽  
Control Group ◽  
Tp53 Mutations ◽  
Multiple Tumor ◽  
Promising Tool ◽  
Next Generation Sequencing Ngs ◽  
The Impact ◽  
Generation Sequencing

3046 Background: ICIs revolutionized aNSCLC treatment. The next challenge lays on the search for predictive markers. Detection of multiple tumor-related genetic alterations through NGS in cell free DNA is a promising tool, provided the limited availability of tumor tissue in most cases. Methods: Between January 2017 and October 2019, aNSCLC pts consecutively referring to our Institution were prospectively screened with plasma NGS while included in two clinical trials: VISION (NCT02864992) and MAGIC trial, an observational study. In VISION trial NGS was performed in plasma (Guardant360 test) and tissue (Oncomine Focus Assay). In MAGIC Myriapod NGS-IL 56G Assay was used. Aim of the study was to evaluate the impact of STK11, KRAS and TP53 mutations (muts) on outcome of ICI-treated pts, with overall survival (OS) as primary endpoint. A control group of pts not receiving ICIs was also analyzed. Results: A total of 235 NSCLC pts were enrolled and received ICIs. 93 pts were analyzed in plasma at the time of beginning ICIs: median OS was 18.9 m (95% CI: 13.7-24.1) and median immune-related progression free disease (irPFS) 3.8 m (95% CI: 2.5-5.1). 49 (52.7%), 22 (23.7%) and 8 (8.6%) pts carried TP53, KRAS and STK11 pathogenic alterations, respectively. STK11 mutated pts showed a trend for worse OS compared with wildtype counterpart (14.9 m, 95% CI: 6.5-23.3, versus 20.3, 95% CI: 13.4-27.2, p = 0.192) KRAS muts had no impact on outcome. Pts with TP53 or STK11/KRAS co-mut (n = 3) had worse OS (12.3 m, 95% CI: 9.2-15.4; HR = 3, 95% CI: 1.6-5.8, p = 0.001 and 5.9 m, 95% CI: 1.4-7.6; HR = 2.9, 95% CI: 1.4-6.3, p = 0.007) and worse irPFS (2.8 m, 95% CI: 1.7-3.9, HR = 1.8 95% CI: 1.1-3.1, p = 0.03 and 1.2 m, 95% CI: 0.9-1.5, HR = 2.2 95% CI: 1.2-4.1, p = 0.01). Number of muts negatively impacts pts’ OS (HR = 1.2, 95% CI: 1.1-1.3, p = 0.02) and was higher among TP53 mutated pts (p < 0.001, Mann-Whitney test). In multivariate analysis, TP53 and STK11/KRAS retained significance. A control group of pts not receiving ICIs was analyzed (n = 101): median OS was 16.8 m (95% CI: 13-20.6). Nor STK11 (n = 10), nor STK11/KRAS (n = 6) had impact on OS (HR = 1.8, 95% CI: 0.7-4.7, p = 0.267 and 1.4, 95% CI: 0.7-3.0, p = 0.293) while the presence of TP53 muts (n = 41) was associated with shorter OS (11.4 m, 95% CI: 7.3-15.5; HR = 2.2, 95% CI: 1.2-4.2, p = 0.009). Conclusions: NGS performed in plasma might be used to detect predictive markers. TP53 muts in plasma at baseline had prognostic value, while STK11/KRAS muts were associated with worse outcome to ICIs.

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