Combined assessment of the TNM stage and BRAF mutational status at diagnosis in sporadic colorectal cancer patients

Oncotarget
José María SayaguésMaría Eugenia Sarasquete

Abstract

The prognostic impact of KRAS mutations and other KRAS-related and non-related genes such as BRAF, NRAS and TP53, on sporadic colorectal cancer (sCRC) remain controversial and/or have not been fully established. Here we investigated the frequency of such mutations in primary sCRC tumors and their impact on patient progression-free survival (PFS) and overall survival (OS). Primary tumor tissues from 87 sCRC patients were analysed using a custom-built next generation sequencing (NGS) panel to assess the hotspot mutated regions of KRAS/NRAS (exons 2, 3 and 4), BRAF (exon 15) and TP53 (all exons). Overall, mutations in these genes were detected in 46/87 sCRC tumors analyzed (53%) with the following frequencies per gene: TP53, 33%; KRAS, 28%; BRAF, 7%; and NRAS, 1%. A significant association was found between KRAS mutations and right side colon tumor location (p=0.05), well-differentiated tumors (p=0.04) and absence of lymphovascular invasion (p=0.05). In turn, BRAF-mutated tumors frequently corresponded to poorly- or moderately-differentiated sCRC (p=0.02) and showed a higher frequency of peritoneal carcinomatosis (p=0.006) and microsatellite instability (p=0.007). From the prognostic point of view, the BRAF mutational status toget...Continue Reading

References

Jan 26, 2005·British Journal of Cancer·A J MunroD P Lane
Apr 16, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hans PrenenSabine Tejpar
Apr 29, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Fotios LoupakisAlfredo Falcone
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Jul 3, 2009·The New England Journal of Medicine·Jolien TolCornelis J A Punt
Feb 18, 2010·International Journal of Cancer. Journal International Du Cancer·Inti ZlobecAlessandro Lugli
Aug 26, 2010·Diagnostic Molecular Pathology : the American Journal of Surgical Pathology, Part B·Natsumi IraharaShuji Ogino
Dec 8, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Shuji OginoCharles S Fuchs
Aug 23, 2012·PloS One·María González-GonzálezJosé María Sayagués
Nov 28, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Marc PeetersJeffrey Wiezorek
Jan 26, 2013·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Christophe RostyDaniel D Buchanan
May 11, 2013·British Journal of Cancer·V EklöfR Palmqvist
Sep 13, 2013·The New England Journal of Medicine·Jean-Yves DouillardScott D Patterson
May 9, 2014·International Journal of Cancer. Journal International Du Cancer·Marta SchirripaAlfredo Falcone
Sep 16, 2014·International Journal of Cancer. Journal International Du Cancer·Jacques FerlayFreddie Bray
Jan 7, 2015·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
Feb 17, 2015·Future Oncology·Luisa FoltranGianpiero Fasola
Oct 3, 2015·Pathology, Research and Practice·Yi ZhouYili Wang
Jun 30, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·David BarrasMauro Delorenzi
Aug 30, 2016·World Journal of Gastroenterology : WJG·Cristiana Lo NigroMarco C Merlano
Sep 28, 2016·Journal of Cancer Research and Clinical Oncology·Yu NakajiYoshihiko Maehara
Oct 16, 2016·Journal of Translational Medicine·Grazia PalombaGiuseppe Palmieri
Nov 7, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Matthew G SummersJeremy P Cheadle
Nov 24, 2016·International Journal of Cancer. Journal International Du Cancer·Annika ÅlgarsRaija Ristamäki
Dec 21, 2016·Annals of Oncology : Official Journal of the European Society for Medical Oncology·J F SeligmannG Middleton
Jan 4, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Vishal DasMintu Pal
Jan 14, 2017·Cancer Science·Tamotsu SugaiHiromu Suzuki

❮ Previous
Next ❯

Citations

Mar 29, 2019·Expert Opinion on Biological Therapy·Celine DebeuckelaereFotios Loupakis
Jan 2, 2019·Gastroenterology Research and Practice·Catherine E Bond, Vicki L J Whitehall

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
biopsy
surgical resection
DNA
Assay

Software Mentioned

Integrative Genomics Viewer
Variant Studio Software
IGV
Genome Analysis Tool Kit ( GATK )
MiSeq Reporter (
SPSS
Variant Studio
MiSeq integrated Aligner ( BWA )
Integrative Genomics Viewer ( IGV )
Illumina studio

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.