Microsatellite Instability Affecting the T17 Repeats in Intron 8 of HSP110, as Well as Five Mononucleotide Repeats in Patients with Colorectal Carcinoma

Abstract

Aim: To investigate mononucleotide markers: BAT-25, BAT-26, NR-21, NR-22 and NR-24 in patients with colorectal cancer (CRC), and the status of HSP110T₁₇, KRAS, BRAF and the MLH1 promoter mutations in microsatellite unstable CRC. Methods: Genetic assessments were performed on samples obtained following resection of CRC in 200 patients. Results: Allelic variations of HSP110T₁₇ were found in all 18 patients with microsatellite instabilities (MSIs) in at least three markers (high-frequency MSI). By contrast, mutations of HSP110T₁₇ were absent in all 20 patients with no MSI frequency. Eight out of 182 patients with low (instability in one marker) or no frequency MSI had allelic shifts due to polymorphisms of BAT-25 (1.5%), NR-21 (1.75%) and NR-24 (1.5%). BRAF mutations were associated with >5 bp shortening of HSP110T₁₇. Conclusion: Patients with high-frequency MSI CRC had allelic variations of HSP110T₁₇. BRAF mutations occur along with greater shortening in HSP110T₁₇ during oncogenesis via the MSI pathway.

KEYWORDS::

• colorectal cancer
• HSP110 heat-shock proteins
• microsatellite instability
• mononucleotide repeats
• pentaplex PCR

Financial & competing interests disclosure

This work was supported by the Ministry of Science, Republic of Serbia, grant number 41033. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by the Ministry of Science, Republic of Serbia, grant number 41033. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.