Constitutional variants in POT1, TERF2IP, and ACD genes in patients with melanoma in the Polish population

Malińska, Karolina; Deptuła, Jakub; Rogoża-Janiszewska, Emilia; Górski, Bohdan; Scott, Rodney J.; Rudnicka, Helena; Kashyap, Aniruddh; Domagała, Paweł; Hybiak, Jolanta; Masojć, Bartłomiej; Cybulski, Cezary; Kram, Andrzej; Boer, Magdalena; Kiedrowicz, Magdalena; Lubiński, Jan; Dębniak, Tadeusz

doi:10.1097/cej.0000000000000633

Cited by 3 publications

(3 citation statements)

References 26 publications

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“…Mutation Taster evaluates mutation effect on protein function and structure. It considers the effect of mRNA expression or splicing (Malińska, et al, 2020). It predicts the disease potential of an alteration as disease causing which is probably deleterious, disease-causing automatic which is deleterious, polymorphism which is probably harmless, and polymorphism automatic which is harmless.…”

Section: Resultsmentioning

confidence: 99%

Analyzing Colorectal Cancer at the Molecular Level through Next-generation Sequencing in Erbil City

Qadir,

Abdoulrahman

2024

ARO

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Colorectal cancer (CRC) ranks as the third leading cause of cancer-related deaths globally. It is characterized as a genomic disorder marked by diverse genomic anomalies, including point mutations, genomic rearrangements, gene fusions, and alterations in chromosomal copy numbers. This research aims to identify previously undisclosed genetic variants associated with an increased risk of CRC by employing next-generation sequencing technology. Genomic DNA was extracted from blood specimens of five CRC patients. The sequencing data of the samples are utilized for variant identification. In addition, the Integrative Genomic Viewer software (IGV) is used to visualize the identified variants. Furthermore, various in silico tools, including Mutation Taster and Align GVGD, are used to predict the potential impact of mutations on structural features and protein function. Based on the findings of this research, 12 different genetic variations are detected among individuals with CRC. Inherited variations are located within the following genes: MSH6, MSH2, PTPRJ, PMS2, TP53, BRAF, APC, and PIK3CA.

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Section: Resultsmentioning

confidence: 99%

Analyzing Colorectal Cancer at the Molecular Level through Next-generation Sequencing in Erbil City

Qadir,

Abdoulrahman

2024

ARO

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“…ACD loss of function (LOF) mutations predispose to melanoma and a broader spectrum of cancers [ 59 ]. Despite the fact that no RCCs were reported in ACD carriers to date [ 59 , 60 , 61 ], a meta-analysis suggested that individuals with an inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma [ 62 ]. Two other cases respectively harbored a novel 14-base-pair deletion (c.2228_2240del p.(Q743fs)) and a rare missense VUS (rs1588304158) in TSC1 .…”

Section: Resultsmentioning

confidence: 99%

The PI3K/mTOR Pathway Is Targeted by Rare Germline Variants in Patients with Both Melanoma and Renal Cell Carcinoma

Hubert

Suybeng

Vallée

et al. 2021

Cancers

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Background: Malignant melanoma and RCC have different embryonic origins, no common lifestyle risk factors but intriguingly share biological properties such as immune regulation and radioresistance. An excess risk of malignant melanoma is observed in RCC patients and vice versa. This bidirectional association is poorly understood, and hypothetic genetic co-susceptibility remains largely unexplored. Results: We hereby provide a clinical and genetic description of a series of 125 cases affected by both malignant melanoma and RCC. Clinical germline mutation testing identified a pathogenic variant in a melanoma and/or RCC predisposing gene in 17/125 cases (13.6%). This included mutually exclusive variants in MITF (p.E318K locus, N = 9 cases), BAP1 (N = 3), CDKN2A (N = 2), FLCN (N = 2), and PTEN (N = 1). A subset of 46 early-onset cases, without underlying germline variation, was whole-exome sequenced. In this series, thirteen genes were significantly enriched in mostly exclusive rare variants predicted to be deleterious, compared to 19,751 controls of similar ancestry. The observed variation mainly consisted of novel or low-frequency variants (<0.01%) within genes displaying strong evolutionary mutational constraints along the PI3K/mTOR pathway, including PIK3CD, NFRKB, EP300, MTOR, and related epigenetic modifier SETD2. The screening of independently processed germline exomes from The Cancer Genome Atlas confirmed an association with melanoma and RCC but not with cancers of established differing etiology such as lung cancers. Conclusions: Our study highlights that an exome-wide case-control enrichment approach may better characterize the rare variant-based missing heritability of multiple primary cancers. In our series, the co-occurrence of malignant melanoma and RCC was associated with germline variation in the PI3K/mTOR signaling cascade, with potential relevance for early diagnostic and clinical management.

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“…The most frequent missense mutation was observed in endometrial carcinoma, melanoma, and esophageal squamous cell carcinoma ( Figure 2 a). The abovementioned genetic alterations have been detected in all domains of RAP1 ( Figure 2 b) [ 17 , 18 , 19 , 20 , 21 ]. It is also worth adding that assessment of a gene damage index for all protein-coding genes places RAP1 in the top 20% of human genes concerning mutation intolerance [ 22 ].…”

Section: Rap1 Mutations In Human Diseasementioning

confidence: 99%

RAP1/TERF2IP—A Multifunctional Player in Cancer Development

Deręgowska

Wnuk

2021

Cancers

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Mammalian RAP1 (TERF2IP), the most conserved shelterin component, plays a pleiotropic role in the regulation of a variety of cellular processes, including cell metabolism, DNA damage response, and NF-κB signaling, beyond its canonical telomeric role. Moreover, it has been demonstrated to be involved in oncogenesis, progression, and chemoresistance in human cancers. Several mutations and different expression patterns of RAP1 in cancers have been reported. However, the functions and mechanisms of RAP1 in various cancers have not been extensively studied, suggesting the necessity of further investigations. In this review, we summarize the main roles of RAP1 in different mechanisms of cancer development and chemoresistance, with special emphasis on the contribution of RAP1 mutations, expression patterns, and regulation by non-coding RNA, and briefly discuss telomeric and non-telomeric functions.

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Constitutional variants in POT1, TERF2IP, and ACD genes in patients with melanoma in the Polish population

Cited by 3 publications

References 26 publications

Analyzing Colorectal Cancer at the Molecular Level through Next-generation Sequencing in Erbil City

Analyzing Colorectal Cancer at the Molecular Level through Next-generation Sequencing in Erbil City

The PI3K/mTOR Pathway Is Targeted by Rare Germline Variants in Patients with Both Melanoma and Renal Cell Carcinoma

RAP1/TERF2IP—A Multifunctional Player in Cancer Development

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