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Molecular analysis of gastric cancer identifies discrete subtypes associated with distinct clinical characteristics and survival outcomes: the ACRG (Asian Cancer Research Group) study

ABSTRACT: Molecular analysis of gastric cancer identifies discrete subtypes associated with distinct clinical characteristics and survival outcomes: the ACRG (Asian Cancer Research Group) study

PROVIDER: PRJNA276142 | ENA |

REPOSITORIES: ENA

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Molecular analysis of gastric cancer identifies discrete subtypes associated with distinct clinical characteristics and survival outcomes: the ACRG (Asian Cancer Research Group) study [gastric tumors]

Project description:Gastric cancer, a leading cause of cancer related deaths, is a heterogeneous disease, with little consensus on molecular subclasses and their clinical relevance. We describe four molecular subtypes linked with distinct patterns of molecular alterations, disease progression and prognosis viz. a) Microsatellite Instable: hypermutated intestinal subtype tumors occurring in antrum, best overall prognosis, lower frequency of recurrence (22%), with liver metastasis in 23% of recurred cases b) Mesenchymal-like: diffuse tumors with worst prognosis, a tendency to occur at an earlier age and highest recurrence (63%) with peritoneal seeding in 64% of recurred cases, low frequency of molecular alterations c) TP53-inactive with TP53 loss, presence of focal amplifications and chromosomal instability d) TP53-active marked by EBV infection and PIK3CA mutations. The key molecular mechanisms and associated survival patterns are validated in multiple independent cohorts, to provide a consistent and unified framework for further preclinical and clinical research. ACRG Gastric cohort: microarray profiles from 300 gastric tumors from gastric cancer patients.

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Molecular analysis of gastric cancer identifies discrete subtypes associated with distinct clinical characteristics and survival outcomes: the ACRG (Asian Cancer Research Group) study [normal tissue]

Project description:Gastric cancer, a leading cause of cancer-related deaths, is a heterogeneous disease, with little consensus on molecular subclasses and their clinical relevance. We describe four molecular subtypes linked with distinct patterns of molecular alterations, disease progression and prognosis viz. a) Microsatellite Instable: hypermutated intestinal subtype tumors occurring in antrum, best overall prognosis, lower frequency of recurrence (22%), with liver metastasis in 23% of recurred cases; b) Mesenchymal-like: diffuse tumors with worst prognosis, a tendency to occur at an earlier age and highest recurrence (63%) with peritoneal seeding in 64% of recurred cases, low frequency of molecular alterations; c) TP53-inactive with TP53 loss, presence of focal amplifications and chromosomal instability; and d) TP53-active marked by EBV infection and PIK3CA mutations. The key molecular mechanisms and associated survival patterns are validated in multiple independent cohorts, to provide a consistent and unified framework for further preclinical and clinical research.

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Molecular analysis of gastric cancer identifies discrete subtypes associated with distinct clinical characteristics and survival outcomes: the ACRG (Asian Cancer Research Group) study

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-04-17 | E-GEOD-66229 | biostudies-arrayexpress

Molecular analysis of gastric cancer identifies discrete subtypes associated with distinct clinical characteristics and survival outcomes: the ACRG (Asian Cancer Research Group) study

Project description:This SuperSeries is composed of the SubSeries listed below.

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AMPKα Modulation in Cancer Progression: Multilayer Integrative Analysis of the Whole Transcriptome in Asian Gastric Cancer

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AMPKM-NM-1 Modulation in Cancer Progression: Multilayer Integrative Analysis of the Whole Transcriptome in Asian Gastric Cancer

Project description:Gastric cancer is the most common cancer in Asia and most developing countries. To identify the molecular underpinnings of gastric cancer in the Asian population, we applied an RNA-sequencing approach to gastric tumor and noncancerous specimens to quantitatively characterize the entire transcriptome of gastric cancer (including mRNAs and microRNAs). A multi-layer analysis was then developed to identify multiple types of transcriptional aberrations associated with different stages of gastric cancer, including differentially expressed mRNAs, recurrent somatic mutations and key differentially expressed microRNAs. Through this approach, we identified the central metabolic regulator AMPK-M-NM-1 as a potential functional target in Asian gastric cancer. Further, we experimentally demonstrated the translational relevance of this gene as a potential therapeutic target for early-stage gastric cancer in Asian patients. Together, our findings not only provide a valuable information resource for identifying and elucidating the molecular mechanisms of Asian gastric cancer, but also represent a general integrative framework to develop more effective therapeutic targets. Using Life Technologies SOLiDM-bM-^DM-" sequencing platform, we performed transcriptome-wide profiling of gastric cancer samples from 30 anonymous, unrelated Asians of both sexes. Included were six noncancerous gastric tissue samples and 24 gastric tumor samples that represented stages I through IV of tumor development. From the WT-seq protocol we generated a WT-seq dataset of 2.1 billion 50-nt short reads from the 30 samples; Applying the second small RNA-seq protocol to 19 gastric tumor samples (5 of the original 24 yielded insufficient sample amounts) and 6 noncancerous gastric tissue samples resulted in a small RNA-seq dataset.

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