KRAS mutations in microsatellite instable gastric tumours: impact of targeted treatment and intratumoural heterogeneity

Virchows Archiv : an International Journal of Pathology
Pedro QueirósCarla Oliveira

Abstract

In gastric cancer (GC), epidermal growth factor receptor (EGFR) overexpression associates with poor prognosis. Addition of a chimeric monoclonal antibody against EGFR (cetuximab) to first-line treatment of metastatic colorectal tumours improved outcomes of patients (stratified for KRAS wild-type cancers), whereas GC patients did not benefit from this approach. In GC, however, stratification based on KRAS mutations was not performed, and the 30 % KRAS mutation frequency in microsatellite instable cancers (MSI), which represents ∼4 % of total GC, was disregarded. Further, intratumoural heterogeneity regarding KRAS mutant subpopulations might also contribute to anti-EGFR therapy failure. We assessed the mutational status of the entire KRAS coding sequence in 19 MSI-GC cases by multiplex PCR/sequencing and used peak height ratio determined from electropherograms from KRAS heterozygous mutants and histopathological evaluation to infer tumour heterogeneity in GC. Using 2 multiplex reactions per sample, we found that 26 % (5/19) of MSI-GC cases harboured KRAS mutations (2 G12D, 2 G13D, 1 G12V). No mutations were found outside the codon 12 and 13 hotspots. Our analysis supported the co-existence of KRAS-positive and KRAS-negative tumou...Continue Reading

References

Oct 29, 1997·Proceedings of the National Academy of Sciences of the United States of America·S OlschwangG Thomas
Apr 6, 2001·The American Journal of Pathology·W S SamowitzM L Slattery
Oct 13, 2001·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·R I NicholsonM E Harper
Oct 14, 2003·Gastroenterology·Caroline BrennetotSimo Schwartz
Jul 5, 2005·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Sérgia VelhoRaquel Seruca
Mar 28, 2006·Nature Genetics·Carlo C MaleyBrian J Reid
Nov 17, 2006·Nature Reviews. Cancer·Lauren M F MerloCarlo C Maley
Dec 17, 2009·Laboratory Investigation; a Journal of Technical Methods and Pathology·Minghong JiangDaru Lu
Apr 20, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Eric Van CutsemFortunato Ciardiello
Jun 23, 2012·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·Fernando RiveraUNKNOWN SEOM (Spanish Society of Clinical Oncology)
Jul 20, 2012·Nature·UNKNOWN Cancer Genome Atlas Network
Apr 4, 2013·Science Signaling·Jianjiong GaoNikolaus Schultz
Apr 19, 2013·The Lancet Oncology·Florian LordickUNKNOWN Arbeitsgemeinschaft Internistische Onkologie and EXPAND Investigators
Mar 22, 2014·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Ana FerroNuno Lunet
Mar 25, 2014·Cancer Treatment Reviews·Florian LordickAndrés Cervantes
Aug 1, 2014·Nature·UNKNOWN Cancer Genome Atlas Research Network
Sep 6, 2014·Annals of Oncology : Official Journal of the European Society for Medical Oncology·E Van CutsemUNKNOWN ESMO Guidelines Working Group
Sep 25, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Pierre Laurent-PuigValerie Taly
Feb 5, 2015·BMC Gastroenterology·Phillip StahlAndreas H Marx
Feb 6, 2015·CA: a Cancer Journal for Clinicians·Lindsey A TorreAhmedin Jemal
Apr 9, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·N NormannoUNKNOWN CAPRI-GOIM investigators

❮ Previous
Next ❯

Citations

Apr 12, 2016·PloS One·Peter JoJochen Gaedcke
Nov 9, 2017·Pathology Oncology Research : POR·Karol PolomFranco Roviello
Nov 20, 2016·Scientific Reports·Chaoying YouYi Ba
May 22, 2019·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Lindsay C HewittHeike I Grabsch

❮ Previous
Next ❯

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.

© 2021 Meta ULC. All rights reserved