Background
Stomach cancer is the third deadliest among all cancers worldwide. Although incidence of the intestinal-type gastric cancer has decreased, the incidence of diffuse-type is still increasing and its progression is notoriously aggressive. There is insufficient information on genome variations of diffuse-type gastric cancer because its cells are usually mixed with normal cells, and this low cellularity has made it difficult to analyze the genome.
#1Patrícia Carneiro(Institute of Molecular Pathology and Immunology of the University of Porto)H-Index: 7
#2Joana Figueiredo(Institute of Molecular Pathology and Immunology of the University of Porto)H-Index: 23
Last. Raquel Seruca(Institute of Molecular Pathology and Immunology of the University of Porto)H-Index: 80
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Introduction: Epithelial cadherin (E-cadherin) plays a key role in epithelial cell-cell adhesion, contributing to tissue differentiation and homeostasis. Throughout the past decades, research has shed light on the molecular mechanisms underlying E-cadherin's role in tumor progression, namely in invasion and metastization. Emerging evidence established E-cadherin as a tumor suppressor and suggests that targeting E-cadherin or downstream signaling molecules may constitute effective cancer therapeu...
It is well documented that germline mutations in the E-cadherin (CDH1) gene are linked to hereditary diffuse gastric cancer (HDGC). Despite the known molecular genetic causes, most gastric cancers are sporadic and poorly investigated for susceptibility genes. We report the finding of a novel germline missense mutation in exon 6, c. 820 G > A (p.G274S) in one sporadic gastric cancer patient. This new variant does not affect cryptic splicing of CDH1 as demonstrated by molecular assay. Immunohistoc...
#1Vivian Y. Chang(UCLA: University of California, Los Angeles)H-Index: 10
#2Noah Federman(UCLA: University of California, Los Angeles)H-Index: 27
Last. Stanley F. Nelson(UCLA: University of California, Los Angeles)H-Index: 103
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Background Gastric adenocarcinoma is a rare diagnosis in childhood. A 14-year old male patient presented with metastatic gastric adenocarcinoma, and a strong family history of colon cancer. Clinical sequencing of CDH1 and APC were negative. Whole exome sequencing was therefore applied to capture the majority of protein-coding regions for the identification of single-nucleotide variants, small insertion/deletions, and copy number abnormalities in the patient’s germline as well as primary tumor.
Last. Kenneth W. Kinzler(HHMI: Howard Hughes Medical Institute)H-Index: 227
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Over the past decade, comprehensive sequencing efforts have revealed the genomic landscapes of common forms of human cancer. For most cancer types, this landscape consists of a small number of “mountains” (genes altered in a high percentage of tumors) and a much larger number of “hills” (genes altered infrequently). To date, these studies have revealed ~140 genes that, when altered by intragenic mutations, can promote or “drive” tumorigenesis. A typical tumor contains two to eight of these “driv...
Purpose The prognosis of gastric cancer (GC) is poor, and the molecular pathogenesis players are vastly unknown. Surgery remains the primary option in GC treatment. The aim of this study was to investigate the impact of somatic CDH1 alterations in prognosis and survival of patients with GC. Patients and Methods A series of patients with sporadic and familial GC (diffuse and intestinal; n = 246) were analyzed for somatic CDH1 mutations, promoter hypermethylation, and loss of heterozygosity (LOH) ...
Neuroblastoma is a malignancy of the developing sympathetic nervous system that often presents with widespread metastatic disease, resulting in survival rates of less than 50%. To determine the spectrum of somatic mutation in high-risk neuroblastoma, we studied 240 affected individuals (cases) using a combination of whole-exome, genome and transcriptome sequencing as part of the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative. Here we report a low median ...
#1Mark Wade(IIT: Istituto Italiano di Tecnologia)H-Index: 25
#2Yao-Cheng Li(Salk Institute for Biological Studies)H-Index: 9
Last. Geoffrey M. Wahl(Salk Institute for Biological Studies)H-Index: 90
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The MDM2 and MDMX (also known as HDMX and MDM4) proteins are deregulated in many human cancers and exert their oncogenic activity predominantly by inhibiting the p53 tumour suppressor. However, the MDM proteins modulate and respond to many other signalling networks in which they are embedded. Recent mechanistic studies and animal models have demonstrated how functional interactions in these networks are crucial for maintaining normal tissue homeostasis, and for determining responses to oncogenic...
The only gastric cancer (GC) syndrome with a proven inherited defect is designated as hereditary diffuse gastric cancer (HDGC) and is caused by germline E-cadherin/CDH1 alterations. Other E-cadherin-associated hereditary disorders have been identified, encompassing HDGC families with or without cleft-lip/palate involvement, isolated early-onset diffuse GCs, and lobular breast cancer families without GC. To date, 141 probands harboring more than 100 different germline CDH1 alterations, mainly poi...
#2Denis Bertrand(Genome Institute of Singapore)H-Index: 25
Last. Yijun Ruan(Genome Institute of Singapore)H-Index: 70
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Background Gastric cancer is the second highest cause of global cancer mortality. To explore the complete repertoire of somatic alterations in gastric cancer, we combined massively parallel short read and DNA paired-end tag sequencing to present the first whole-genome analysis of two gastric adenocarcinomas, one with chromosomal instability and the other with microsatellite instability.
#2Xiaoming Dai(BIDMC: Beth Israel Deaconess Medical Center)H-Index: 8
Last. Wenyi Wei(BIDMC: Beth Israel Deaconess Medical Center)H-Index: 67
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Abstract RING-in-between-RING (RBR) E3 ligases are one class of E3 ligases that is characterized by the unique RING-HECT hybrid mechanism to function with E2s to transfer ubiquitin to target proteins for degradation. Emerging evidence has demonstrated that RBR E3 ligases play an essential role in neurodegenerative diseases, infection, inflammation and cancer. Accumulated evidence has revealed that RBR E3 ligases exert their biological functions in various types of cancers by modulating the degra...
Abstract Objective Bulk tissue genomic analysis of meningiomas identified common somatic mutations, however, it often excluded blood-related variants. In contrast, genomic characterisation of primary cell lines that can provide critical information regarding growth and proliferation, have been rare. In our work, we identified the variants that are present in the blood, tissues and corresponding cell lines that are likely to be predictive, tumorigenic and progressive. Method Whole-exome sequencin...
Last. Lisong Teng(ZJU: Zhejiang University)H-Index: 26
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Gastric cancer (GC) is a leading cause of worldwide cancer-related death. Being a highly heterogeneous disease, the current treatment of GC has been suboptimal due to the lack of subtype-dependent therapies. Peritoneal dissemination (PD) is a common pattern of GC metastasis associated with poor prognosis. Therefore, it is urgently necessary to identify patients at high risk of PD. PD is found to be associated with Lauren diffuse type GC. Molecular profiling of GC, especially diffuse type GC, has...
#1Xiaoyun Zhou(Peking Union Medical College Hospital)H-Index: 6
#2Xiaohui Xu(Peking Union Medical College Hospital)H-Index: 4
Last. Yushang Cui(Peking Union Medical College Hospital)H-Index: 5
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PURPOSE NSCLC is the most common type of lung cancers. The purpose of this study is to screen cancer-related mutations in early LUAD in China through NGS technology, determine their correlation with clinical characteristics and provide basis for treatment decisions. METHODS In this study, we performed a 583 gene panel to detect the mutational spectrum of the tumors which were collected from 98 LUAD patients. The sequencing data and clinical characteristics were analyzed. RESULTS Mutations were i...
Pathogenic variants in CDH1, encoding epithelial cadherin (E-cadherin), have been implicated in hereditary diffuse gastric cancer (HDGC), lobular breast cancer, and both syndromic and non-syndromic cleft lip/palate (CL/P). Despite the large number of CDH1 mutations described, the nature of the phenotypic consequence of such mutations is currently not able to be predicted, creating significant challenges for genetic counselling. This study collates the phenotype and molecular data for available C...
#1Seungyeul Yoo(ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 12
#2Quan Chen(ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 1
Last. Jun Zhu(ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 65
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Gastric cancer (GC) is a heterogeneous disease of diverse genetic, genomic, and epigenetic alterations. Tumor microenvironment (TME) also contributes to the heterogeneity of GC. To investigate GC heterogeneity, we developed an Integrative Sequential Causality Test (ISCT) to identify key regulators of GC by integrating DNA methylation, copy number variation, and transcriptomic data. Applying ISCT to three GC cohorts containing methylation, CNV and transcriptomic data, 11 common methylation-driven...
#2Ralph H. Hruban(JHUSOM: Johns Hopkins University School of Medicine)H-Index: 208
Next-generation sequencing has expanded our understanding of the molecular alterations that occur in tumors of the pancreas and stomach, and it is now becoming clear that new histologic and molecular-based classification systems are possible. These systems do not replace, but instead complement, the morphologic classification systems that have been developed and tested by pathologists over many decades. Importantly, new classification systems integrate morphology and molecular findings into cohe...
#1Wenyi Luo(University of Texas MD Anderson Cancer Center)H-Index: 7
#2Faysal Fedda(University of Texas MD Anderson Cancer Center)H-Index: 6
Last. Dongfeng Tan(University of Texas MD Anderson Cancer Center)H-Index: 3
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Gastric cancer, a group of common malignancies, results in the most cancer mortality worldwide after only lung and colorectal cancer. Although familial gastric cancers have long been recognized, it was not until recently that they were discovered to be associated with mutations of specific genes. Mutations of CDH1, the gene encoding E-cadherin, are the most common germline mutations detected in gastric cancer and underlie hereditary diffuse gastric cancer (HDGC) syndrome. All reported HDGCs are ...
Last. Shengtao Zhu(Capital Medical University)H-Index: 14
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: Lauren classification is a pathology-based gastric cancer (GC) subtyping system, which is widely used in the clinical treatment of patients with GC. However, genome-scale molecular characteristics to distinguish between diffuse (DF) and intestinal (IT) GC remain incompletely characterized, particularly at the transcriptional regulatory level. In the present study, gene regulatory networks were constructed using the Passing Attributes between Networks for Data Assimilation (PANDA) algorithm for...
#1Liza L Cox(Seattle Children's Research Institute)H-Index: 10
#2Timothy C. Cox(Monash University, Clayton campus)H-Index: 33
Last. Tony Roscioli(UNSW: University of New South Wales)H-Index: 31
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Non-syndromic cleft lip with or without cleft palate (NS-CL/P) is one of the most common human birth defects and is generally considered a complex trait. Despite numerous loci identified by genome-wide association studies, the effect sizes of common variants are relatively small, with much of the presumed genetic contribution remaining elusive. We report exome-sequencing results in 209 people from 72 multi-affected families with pedigree structures consistent with autosomal-dominant inheritance ...