Plasma-SeqSensei™ Colorectal Cancer RUO Kit

Plasma-SeqSensei™ (PSS) CRC RUO Kit allows the highly sensitive and specific detection of mutations in circulating tumour DNA (ctDNA) from plasma of patients with colorectal cancer (CRC).

The kit is based on the next-generation sequencing technology and covers key mutations of the MAPK signaling genes KRAS, NRAS and BRAF and the PIK3CA genes. These genes significantly contribute to the development of colorectal cancer and are important biomarkers utilised for prognosis, choice of therapy, as well as monitoring of recurrence and therapy response. [1]

KRAS is mutated in ~40% of all CRC cases (in exon 2, codons 12 (70-80%) and 13 (15-20%)). The remaining mutations are mainly located in exon 3 codons 59-61 and in exon 4 (codons 117 and 146). [2]

Mutations in NRAS are present in ~3-5% of CRC cases (in exon 3 codon 61 (60%) and in exon 2 codons 12, 13). NRAS mutations are normally mutually exclusive to KRAS alterations. [3]

BRAF mutations (overall V600E) occur in 8-12% of mCRC patients and are almost exclusively non-overlapping with RAS mutations. [4-5]

The frequency of PIK3CA mutations in CRC is 7-32% (mutation hotspots are located on exons 9 and 20). [6]

For the configuration of the Plasma-SeqSensei™ CRC RUO kits 4 key cancer genes were selected after comparison of mutation frequencies using the COSMIC (Catalogue of Somatic Mutation in Cancer) and cBioPortal for cancer genomics databases.

Features

Mutation frequencies are listed in the table below:

Colorectal cancer

  COSMIC [7] cBioPortal [8]
BRAF 12.4% 12.0%
KRAS 33.3% 40.0%
NRAS 3.7% 5.0%
PIK3CA 12.1% 21.0%

 

Most frequent mutations detected by Plasma-SeqSensei™ CRC RUO panel:

Gene Most frequent mutations in CRC
BRAF V600E
KRAS G12D, G12V, G13D, G12C, G12A, G12S, G12R, A146T, G13C, Q61H
NRAS Q61K, G12D   
PIK3CA E545K, H1047R, E542K, Q546K

Plasma-SeqSensei™ CRC RUO Kit is intended for research use only. Diagnostic use is not supported

 

References

  1. Lee et al. Current and emerging biomarkers in metastatic colorectal cancer. Current Oncology 26, 7-15, 2019.
  2. Troiani et al. RAS IN COLORECTAL CANCER: ESMO BIOMARKER FACTSHEET. 2015.
  3. Bos et al. Prevalence of ras gene mutations in human colorectal cancers. Nature 327, 293-297, 1987.
  4. Davies et al. Mutations of the BRAF gene in human cancer. Nature 417, 949-954, 2002
  5. Venderbosch at al. Mismatch repair status and BRAF mutation status in metastatic colorectal cancer patients: a pooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS studies. Clin Cancer Res 20, 5322-5330, 2014.
  6. Wang et al. PIK3CA mutations confer resistance to first-line chemotherapy in colorectal cancer. Cell Death and Disease 9, 1-11, 2018.
  7. https://cancer.sanger.ac.uk/cosmic
  8. https://www.cbioportal.org/
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