A Pilot Study of Baseline Spatial Genomic Heterogeneity in Primary Gastric Cancers Using Multi-Region Endoscopic Sampling

Frontiers in Oncology
J ChaoHyuk Lee

Abstract

Intertumoral heterogeneity among actionable biomarkers including ERBB2, FGFR2 and EGFR has been observed to occur under therapeutic pressure in advanced gastric cancer. However, baseline intratumoral heterogeneity at diagnosis is understudied and may impact clinical outcomes. We sought to explore intratumoral heterogeneity in primary advanced gastric cancers via DNA sequencing from multi-region endoscopic sampling at diagnosis. Patients with newly diagnosed advanced gastric adenocarcinoma underwent endoscopic mapping and pre-determined 8-sector biopsy of the primary tumor with concurrent plasma cfDNA sampling. Biopsy samples were subjected to targeted next generation sequencing and plasma cfDNA was analyzed via a 28-gene cfDNA assay. Expectedly, we observed that the majority of genetic alterations were shared among multi-sector biopsies within the same gastric primary tumor. However, all samples contained private subclonal alterations between biopsy sectors, including actionable alterations in GNAS and STK11. Cell free DNA analyses also exhibited both shared and non-shared alterations between mutations detected in cfDNA and tumor tissue biopsies confirming baseline intertumoral heterogeneity. This is the first dataset to confir...Continue Reading

References

Nov 17, 2006·Nature Reviews. Cancer·Lauren M F MerloCarlo C Maley
Sep 30, 2010·Proceedings of the National Academy of Sciences of the United States of America·Ivana BozicMartin A Nowak
Jan 20, 2012·Nature·Mel Greaves, Carlo C Maley
Mar 9, 2012·The New England Journal of Medicine·Marco GerlingerCharles Swanton
Aug 1, 2014·Nature·UNKNOWN Cancer Genome Atlas Research Network
Mar 25, 2015·Human Pathology·Rocco CappellessoMassimo Rugge
Apr 27, 2017·The New England Journal of Medicine·Mariam Jamal-HanjaniUNKNOWN TRACERx Consortium
Apr 27, 2017·Nature·Christopher AbboshCharles Swanton
Oct 6, 2017·Cancer Discovery·Eirini PectasidesDaniel V Catenacci
Dec 8, 2017·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M YangW Zhang
Feb 7, 2018·Annals of Oncology : Official Journal of the European Society for Medical Oncology·S T KimJ Lee
Feb 10, 2018·Nature Reviews. Cancer·Kent W HunterLalage Wakefield
Feb 21, 2018·Annals of Oncology : Official Journal of the European Society for Medical Oncology·S J Klempner, J Chao
Apr 17, 2018·Cell·Thomas J MitchellUNKNOWN TRACERx Renal Consortium
Apr 17, 2018·Cell·Samra TurajlicUNKNOWN TRACERx Renal Consortium
Apr 17, 2018·Cell·Samra TurajlicUNKNOWN TRACERx Renal Consortium

❮ Previous
Next ❯

Methods Mentioned

BETA
biopsies
biopsy
Assay
exome sequencing
surgical resection
PCR

Software Mentioned

Archer Analysis

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.