Germline variants in cancer therapy

Kaehler, Meike; Cascorbi, Ingolf

doi:10.20517/cdr.2019.05

Cited by 4 publications

(5 citation statements)

References 109 publications

(115 reference statements)

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“…The article by Kaehler and Cascorbi [ 10 ] focuses on a relevant distinction in cancer pharmacogenetics. Cancer pharmacogenetics and pharmacogenomics imply in fact a complex conundrum of germline variants from normal cells and somatic mutations from tumor cells.…”

mentioning

confidence: 99%

“Pharmacogenetics of Cancer” - Cancer Drug Resistance special issue

Mini¹,

Nobili²

2020

CDR

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A companion diagnostic device can be in vitro diagnostic device or an imaging tool that provides information that is essential for the safe and effective use of a corresponding therapeutic product. The use of an IVD companion diagnostic device with a specific therapeutic product is stipulated in the instructions for use in the labeling of both the diagnostic device and the corresponding therapeutic product, as well as in the labeling of any generic equivalents and biosimilar equivalents of the therapeutic product. This table lists devices in the order of approval, with most recently approved device at the top.

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mentioning

confidence: 99%

“Pharmacogenetics of Cancer” - Cancer Drug Resistance special issue

Mini¹,

Nobili²

2020

CDR

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“…Germline mutations are well-recognized for their role in cancer predisposition (Chatrath et al, 2020) and prediction of adverse events of certain chemotherapies (pharmacogenetics) (Kaehler & Cascorbi, 2019; O’Donnell & Ratain, 2012). In contrast, evidence regarding the predictive value of germline mutations in drug efficacy or their possible effects in the pathophysiology of tumor progression is widely lacking (Vali-Pour et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Characterization of the mutational landscape of high-grade gliomas in a Latin American cohort

Fernández-Gajardo,

Urra,

Saéz

et al. 2023

Preprint

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BackgroundGlioblastoma, an aggressive form of high-grade glioma, exhibits variations in the incidence and mortality patterns between populations of different ancestry. However, Hispanic and Latino populations remain largely underrepresented in studies of molecular characterization. Here we characterized the mutagenic landscape of high-grade gliomas within a Chilean population focusing on well characterized genetic variants associated with glioblastoma classification, progression, and prognosis.MethodsWe conducted a targeted genomic analysis using next-generation sequencing techniques in 70 Chilean patients with high-grade gliomas from a national single-center referral institution. We focused on the most relevant molecular markers such as isocitrate dehydrogenase 1/2 (IDH) mutations, telomerase reverse transcriptase promoter (TERTp) mutations, histone 3 (H3) gene family mutations, TP53 and PTEN mutations, epidermal growth factor receptor (EGFR) gene amplification, and cyclin-dependent kinase inhibitor 2A (CDKN2A) deletions. Survival analyses were performed to assess the clinical relevance of these markers and their impact on patient prognosis. Additionally, due to our interest in the role of proteostasis and glioblastoma, we investigated possible ERN1 variants in our Chilean cohort.ResultsOur findings mostly align with other international cohorts of non-Latin-American origin, confirming the importance of established molecular markers in glioblastoma. Notably, we identified novel TP53 and PTEN mutations with a predicted damaging effect, expanding the genetic spectrum of alterations in these brain tumors. Furthermore, a lower-than-expected mutation rate in the NF1 gene was observed, emphasizing a distinctive genetic profile of glioblastoma in this Latin American population. Prognostic assessments based on TERT promoter and IDH mutations mirrored previous studies on non-Latino American and European populations. Of note, we identified the germline ERN1 variant rs139229826 in 11% of our patient cohort, a variant previously unreported in glioblastoma patients.ConclusionThis study underscores the importance of conducting glioblastoma research in underrepresented populations, providing insights into the molecular characteristics of high-grade gliomas within a Latin American context. Our findings contribute to the growing body of evidence suggesting molecular diversity across diverse glioblastoma populations, offering a foundation for future international comparative studies.

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“…Regarding cancer pharmacogenetics, somatic mutations have become druggable targets or biomarkers, whereas germline mutations are potentially responsible for drug responses [ 224 ]. Primary resistance to treatments can be supported by germline splicing variants.…”

Section: Therapeutic Targeting Of Splicing In Cancermentioning

confidence: 99%

Splicing-Disrupting Mutations in Inherited Predisposition to Solid Pediatric Cancer

Alba-Pavón

Alaña

Astigarraga

et al. 2022

Cancers

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The prevalence of hereditary cancer in children was estimated to be very low until recent studies suggested that at least 10% of pediatric cancer patients carry a germline mutation in a cancer predisposition gene. A significant proportion of pathogenic variants associated with an increased risk of hereditary cancer are variants affecting splicing. RNA splicing is an essential process involved in different cellular processes such as proliferation, survival, and differentiation, and alterations in this pathway have been implicated in many human cancers. Hereditary cancer genes are highly susceptible to splicing mutations, and among them there are several genes that may contribute to pediatric solid tumors when mutated in the germline. In this review, we have focused on the analysis of germline splicing-disrupting mutations found in pediatric solid tumors, as the discovery of pathogenic splice variants in pediatric cancer is a growing field for the development of personalized therapies. Therapies developed to correct aberrant splicing in cancer are also discussed as well as the options to improve the diagnostic yield based on the increase in the knowledge in splicing.

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Germline variants in cancer therapy

Cited by 4 publications

References 109 publications

“Pharmacogenetics of Cancer” - Cancer Drug Resistance special issue

“Pharmacogenetics of Cancer” - Cancer Drug Resistance special issue

Characterization of the mutational landscape of high-grade gliomas in a Latin American cohort

Splicing-Disrupting Mutations in Inherited Predisposition to Solid Pediatric Cancer

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