Patients with genetically heterogeneous synchronous colorectal cancer carry rare damaging germline mutations in immune-related genes

Cereda, Matteo; Gambardella, Gennaro; Benedetti, Lorena; Iannelli, Fabio; Patel, Dominic; Basso, Gianluca; Guerra, Rosalinda Fiorella; Mourikis, Thanos P.; Puccio, Ignazio; Sinha, Shruti; Laghi, Luigi; Spencer, Jo; Rodriguez‐Justo, Manuel; Ciccarelli, Francesca D.

doi:10.1038/ncomms12072

Cited by 49 publications

(72 citation statements)

References 72 publications

(94 reference statements)

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“…For example, using MEGA-V, we have identified significantly mutated immune gene sets in individuals with multiple colorectal cancers (Cereda et al , 2016). …”

Section: Discussionmentioning

confidence: 99%

MEGA-V: detection of variant gene sets in patient cohorts

et al. 2016

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SummaryDetecting significant associations between genetic variants and disease may prove particularly challenging when the variants are rare in the population and/or act together with other variants to cause the disease. We have developed a statistical framework named Mutation Enrichment Gene set Analysis of Variants (MEGA-V) that specifically detects the enrichments of genetic alterations within a process in a cohort of interest. By focusing on the mutations of several genes contributing to the same function rather than on those affecting a single gene, MEGA-V increases the power to detect statistically significant associations.Availability and ImplementationMEGA-V is available at https://github.com/ciccalab/MEGASupplementary information Supplementary data are available at Bioinformatics online.

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“…For example, using MEGA-V, we have identified significantly mutated immune gene sets in individuals with multiple colorectal cancers (Cereda et al , 2016). …”

Section: Discussionmentioning

confidence: 99%

MEGA-V: detection of variant gene sets in patient cohorts

et al. 2016

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“…These 4 genes, namely, CTNNB1, HS90B, NMP, and PAPB1 are obtained after verification from NCG (Table 1) [29]. The other 10 genes, namely, 1433Z, TF-65, CSK1, KU70, SF3B3, RL11, RS3A, HNRPU, RL6, RL26 were verified for the association to cancer from extensive literature survey (using Pubmed, scholar etc).…”

Section: Resultsmentioning

confidence: 99%

“…Thus, 14 genes include 10 genes that acquired association to cancer from literature while the other 4 genes from NCG database (Table 1) [29]. Figure 4.…”

Section: Resultsmentioning

confidence: 99%

Identification of Inference Genes in Breast Cancer Network

Chirom¹,

Ali²,

Malik³

et al. 2017

JBM

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Complex breast cancer network constructed from experimentally verified seventy genes, by coordinating standard seven human protein and genome databases, follows hierarchical scale free features. Centrality based method of identification of inferred genes is implemented to this network and has predicted forty nine breast cancer genes, and nineteen non-breast cancer genes. As predicting good candidate genes before experimental analysis will save time and effort both. Fourteen genes out of nineteen are found to involve in various types of cancer and diseases, and five genes are engaged in non-cancer diseases. Some of the inferred genes need proper experimental investigation to understand fundamental roles of these genes in regulating breast cancer network.

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“…Knudson's two-hit hypothesis and recent cancer genomics studies, the importance of inherited germline mutations in carcinogenesis has become clearer (27)(28)(29). Instead of entire profile of germline variants, we restricted our study only to rare and deleterious germline mutations.…”

Section: Spectrum Of Deleterious Germline Variants In the Light Ofmentioning

confidence: 99%

“…Several cancer drivers and progression markers were established in this way. More recently, the cancer research field has begun to understand the importance of rare deleterious germline variants in carcinogenesis and progression (28,29,37). GBC is not among the most heritable types of human cancer, although variability in its ethnic and geographical incidence rates has been partly associated with cancer predisposition (38)(39)(40).…”

Section: Cancer Genomics and Proteomicsmentioning

confidence: 99%

Targeted Gene Sequencing of Gallbladder Carcinoma Identifies High-impact Somatic and Rare Germline Mutations

Yadav

Sarkar

Kumari

et al. 2017

CGP

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Abstract. Background: Gallbladder carcinoma (GBC) isGallbladder carcinoma (GBC) is a type of biliary tract cancer, characterized by rapid progression and high mortality. Significant risk factors for GBC include presence of gallstones, chronic inflammation, anomalous pancreatobiliary ductal junctions, advancing age and female gender (1).Incidence and prevalence of GBC exhibit remarkable ethnic and geographical variability. This variability has been attributed to genetic predisposition and lifestyle habits or environmental exposure. The high incidence of GBC in the Indo-Gangetic belt and its poorly characterized molecular pathology have resulted in its reputation as an enigmatic Indian carcinoma (2). Until 2010, the genomic studies of GBC were limited to scanning a few common mutations in wellknown cancer-associated genes such as tumor protein p53 (TP53) and KRAS proto-oncogene, GTPase (KRAS) (3-5). Advancements in massively parallel sequencing technology, or next-generation sequencing (NGS), have propelled the area of cancer genomics and have greatly improved the understanding of tumorigenesis and tumor evolution linked with disease progression (6, 7). Application of NGS provides a means of high-throughput identification of cancer drivers and other genes that may be clinically relevant and or actionable for precision medicine (6). During the past decade, several large-scale cancer mutational landscape studies have contributed to the understanding of the existence of clonal variability within and across tumors in various common cancer types (8). However, GBC remains one of the understudied cancer types, with only a few studies on a limited number of samples (9-11). These studies and previous candidate gene-sequencing investigations indicate that GBC tumors from patients from different geographic regions may have different genetic architectures, suggesting the need for mutation exploration using a high-throughput NGS approach from varied populations (5, 12).The current treatment for patients with GBC is operative resection. However, resection is limited to cases that present at an early stage. GBCs which have progressed are largely incurable and the treatment mostly relies on focal radiation therapy and/or generic chemotherapy (12). The overall survival rate for patients with advanced GBC (stage 3 and 4) is very poor, and fewer than 10% survive for 5 years post 495 This article is freely accessible online.

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Patients with genetically heterogeneous synchronous colorectal cancer carry rare damaging germline mutations in immune-related genes

Cited by 49 publications

References 72 publications

MEGA-V: detection of variant gene sets in patient cohorts

MEGA-V: detection of variant gene sets in patient cohorts

Identification of Inference Genes in Breast Cancer Network

Targeted Gene Sequencing of Gallbladder Carcinoma Identifies High-impact Somatic and Rare Germline Mutations

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