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Case Reports
. 2020 Mar 23;8(3):67.
doi: 10.3390/biomedicines8030067.

Transcriptomic and Genomic Testing to Guide Individualized Treatment in Chemoresistant Gastric Cancer Case

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Free PMC article
Case Reports

Transcriptomic and Genomic Testing to Guide Individualized Treatment in Chemoresistant Gastric Cancer Case

Alexey Moisseev et al. Biomedicines. .
Free PMC article

Abstract

Gastric cancer is globally the fifth leading cause of cancer death. We present a case report describing the unique genomic characteristics of an Epstein-Barr virus-negative gastric cancer with esophageal invasion and regional lymph node metastasis. Genomic tests were performed first with the stomach biopsy using platforms FoundationOne, OncoDNA, and Oncopanel at Dana Farber Institute. Following neoadjuvant chemotherapy, residual tumor was resected and the stomach and esophageal residual tumor samples were compared with the initial biopsy by whole exome sequencing and molecular pathway analysis platform Oncobox. Copy number variation profiling perfectly matched the whole exome sequencing results. A moderate agreement was seen between the diagnostic platforms in finding mutations in the initial biopsy. Final data indicate somatic activating mutation Q546K in PIK3CA gene, somatic frameshifts in PIH1D1 and FBXW7 genes, stop-gain in TP53BP1, and a few somatic mutations of unknown significance. RNA sequencing analysis revealed upregulated expressions of MMP7, MMP9, BIRC5, and PD-L1 genes and strongly differential regulation of several molecular pathways linked with the mutations identified. According to test results, the patient received immunotherapy with anti-PD1 therapy and is now free of disease for 2 years. Our data suggest that matched tumor and normal tissue analyses have a considerable advantage over tumor biopsy-only genomic tests in stomach cancer.

Keywords: companion diagnostics; expression analysis; gastric cancer; genomic test; immunotherapy; molecular pathway analysis; mutation; platform comparison; stomach adenocarcinoma.

Conflict of interest statement

The authors declare no conflict of interest. The Quantida, Inc. had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
(A,B) Hematoxylin and eosin (H&E) staining shows moderately to poorly differentiated adenocarcinoma. (A) Tumor removed from stomach. (B) Tumor removed from esophagus. (C) Baseline tumor appearance: primary gastric lesion (right arrow) and involved lymph node (left arrow).
Figure 2
Figure 2
Overlap of top 40 activated or downregulated pathways for Stomach tumor (ST), Esophagus tumor (ET), and Stomach tumor biopsy (STB) samples: (A) upregulated pathways and (B) downregulated pathways.
Figure 3
Figure 3
Pathway activation profile of the “Reactome PD-1 signaling Main Pathway” in a stomach tumor sample: mutated genes are circled in red.

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