Abstract 6095: Unique tumor microbiome in microsatellite instability high (MSI-H) colon carcinoma

Vanderbilt, Chad; Keshinro, Ajaratu; Chen, Chin-Tung; Babady, Esther; Berger, Michael F.; Zehir, Ahmet; Ladanyi, Marc; Hechtman, Jaclyn F.; Stadler, Zsofia K.; Shia, Jinru; Weiser, Martin R.

doi:10.1158/1538-7445.am2020-6095

Cited by 4 publications

(4 citation statements)

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“…We also found independent statistical enrichment in a univariate analysis of Lactobacillus in MSI-high tumors in both cohorts. Furthermore, we identified 5 addition bacterial genera enriched in MSI-high GC in one cohort with a trend toward enrichment in the opposing cohort, which correlated with other recent findings in the literature 21 (Fig. 3).…”

Section: Discussionsupporting

confidence: 90%

“…Interestingly, of the bacterial genera that showed a trend toward statistical enrichment in MSI-high GC subtype (Fig. 3), Fusobacterium , Bacteroides , Prevotella , and Streptococcuss , were also found to be enriched in MSI-high type colorectal cancer 21. The distinction of these bacteria within MSI-high GC suggests that either these bacteria play a role in the development of MSI-high tumors, or a unique immune environment exists in MSI-high tumors that leads to a favorable colonization by these microbes.…”

Section: Discussionmentioning

confidence: 97%

“…3), Fusobacterium, Bacteroides, Prevotella, and Streptococcuss, were also found to be enriched in MSI-high type colorectal cancer. 21 The distinction of these bacteria within MSI-high GC suggests that either these bacteria play a role in the development of MSI-high tumors, or a unique immune environment exists in MSI-high tumors that leads to a favorable colonization by these microbes. The relationship between this unique microbiome and MSI status is an important area that warrants further investigation.…”

Section: Microbial Enrichment and The Immune Environment Among Gc Sub...mentioning

confidence: 99%

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A Novel Microbiome Signature in Gastric Cancer

et al. 2022

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Objective: The microbiome is hypothesized to have a significant impact on cancer development. In gastric cancer (GC), Helicobacter pylori is an established class I carcinogen. However, additional organisms in the intratumoral microbiome play an important role in GC pathogenesis and progression. In this study, we characterize the full spectrum of the microbes present within GC and identify distinctions among molecular subtypes. Methods: A microbiome bioinformatics pipeline that is generalizable across multiple next-generation sequencing platforms was developed. Microbial profiles for alpha diversity and enrichment were generated for 2 large, demographically distinct cohorts: (1) internal Memorial Sloan Kettering Cancer Center (MSKCC) and (2) The Cancer Genome Atlas (TCGA) cohorts. A total of 520 GC samples were compared with select tumor-adjacent nonmalignant samples. Microbiome differences among the GC molecular subtypes were identified. Results: Compared with nonmalignant samples, GC had significantly decreased microbial diversity in both MSKCC and TCGA cohorts (P<0.05). Helicobacter, Lactobacillus, Streptococcus, Prevotella, and Bacteroides were significantly more enriched in GC samples when compared with nonmalignant tissue (P<0.05). Microsatellite instability-high GC had distinct microbial enrichment compared with other GC molecular subtypes. Conclusion: Distinct patterns of microbial diversity and species enrichment were identified in patients with GC. Given the varied spectrum of disease progression and treatment response of GC, understanding unique microbial signatures will provide the landscape to explore key microbial targets for therapy.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 97%

Section: Microbial Enrichment and The Immune Environment Among Gc Sub...mentioning

confidence: 99%

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A Novel Microbiome Signature in Gastric Cancer

et al. 2022

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“…Interestingly, EAS and SAS patients in our cohort, who had relatively low rates of MSI GC, also had relatively low proportions of Selenomonas and Fusobacterium, which are known to be elevated in both MSI-high gastric 35 and colon cancer. 53 The lack of significant differences in microbial profiles across ancestry groups in a patient population from the United States suggests that intratumoral microbial differences are driven by environmental and geographic factors. Further studies using a larger sample size are necessary to corroborate our findings.…”

Section: Discussionmentioning

confidence: 99%

Unique Genomic Alterations and Microbial Profiles Identified in Patients With Gastric Cancer of African, European, and Asian Ancestry

et al. 2023

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Introduction: Gastric cancer (GC) is a heterogenous disease with clinicopathologic variations due to a complex interplay of environmental and biological factors, which may affect disparities in oncologic outcomes. Here, we characterize differences in the genetic and microbial profiles of GC in patients of African, European, and Asian ancestry. Methods: We identified 1,042 GC patients with next-generation sequencing (NGS) data from an institutional Integrated Mutation Profiling of Actionable Cancer Targets (IMPACT) assay and the Cancer Genomic Atlas (TCGA) group. Genetic ancestry was inferred from markers captured by the IMPACT and TCGA whole exome sequencing panels. Tumor microbial profiles were inferred from sequencing data using a validated microbiome bioinformatics pipeline. Genomic alterations and microbial profiles were compared between GC patients of different ancestries. Results: We assessed 8,023 genomic alterations. The most frequently altered genes were TP53, ARID1A, KRAS, ERBB2, and CDH1. Patients of African ancestry had a significantly higher rate of CCNE1 alterations and a lower rate of KRAS alterations (P<0.05), and patients of East Asian ancestry had a significantly lower rate of PI3K pathway alterations (P<0.05) compared to other ancestries. Microbial diversity and enrichment did not differ significantly across ancestry groups (P>0.05). Discussion: Distinct patterns of genomic alterations and variations in microbial profiles were identified in GC patients of African, European, and Asian ancestry. Our findings of variation in the prevalence of clinically actionable tumor alterations among ancestry groups suggest that precision medicine can mitigate oncologic disparities.

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