Clinicopathological features of Egyptian colorectal cancer patients regarding somatic genetic mutations especially in KRAS gene and microsatellite instability status: a pilot study

Abstract

Background: Colorectal cancer (CRC) is the third most common cause of cancer-related deaths which contributes to a significant public health problem worldwide with 1.8 million new cases and almost 861,000 deaths in 2018 according to the World Health Organization. It exhibits 7.4% of all diagnosed cancer cases in the region of the Middle East and North Africa. Molecular changes that happen in CRCs are chromosomal instability, microsatellite instability (MSI), and CpG island methylator phenotype. The human RAS family (KRAS, NRAS, and HRAS) is the most frequently mutated oncogenes in human cancer appearing in 45% of colon cancers. Determining MSI status across CRCs offers the opportunity to identify patients who are likely to respond to targeted therapies such as anti-PD-1. Therefore, a method to efficiently determine MSI status for every cancer patient is needed. Results: KRAS mutations were detected in 31.6% of CRC patients, namely in older patients (p = 0.003). Codons 12 and 13 constituted 5/6 (83.3%) and 1/6 (16.7%) of all KRAS mutations, respectively. We found three mutations G12D, G12C, and G13D which occur as a result of substitution at c.35G>A, c.34G>T, and c.38G>A and have been detected in 4/6 (66.6%), 1/6 (16.7%), and 1/6 (16.7%) patients, respectively. Eleven (57.9%) patients had microsatellite instability-high (MSI-H) CRC. A higher percentage of MSI-H CRC was detected in female patients (p = 0.048). Eight patients had both MSI-H CRC and wild KRAS mutation with no statistical significance was found between MSI status and KRAS mutation in these studied patients. Conclusion: In conclusion, considering that KRAS mutations confer resistance to EGFR inhibitors, patients who have CRC with KRAS mutation could receive more tailored management by defining MSI status. MSI-high patients have enhanced responsiveness to anti-PD-1 therapies. Thus, the question arises as to whether it is worth investigating this association in the routine clinical setting or not. Further studies with a larger number of patients are needed to assess the impact of MSI status on Egyptian CRC care.

Deep Next Generation Sequencing Identifies Somatic Mutational Signature in Egyptian Colorectal Cancer Patients

“…Matching with a recent study by Kassem et al [19] on the Egyptian CRC patients, we found ve TP53 somatic mutations; c.1024C > T, c.844C > T, c.743G > A, c.524G > A and 215C > G in our CRC group which might reveal that such variants are Egyptian speci c and explain their contribution in colon cancer disease progression as a driver mutation in tumor development.…”

High Probability of Lynch Syndrome among colorectal cancer patients in Indonesia is associated with higher occurrence of KRAS and PIK3CA mutations

“…We previously reported a lower frequency of BRAF mutations (20.45%) in this MSI-CRC cohort [6], similar to what has been reported in China [47][48][49]. This is unlike a common dogma in which KRAS mutation is more associated with MSS while BRAF mutation is associated with MSI [50,51]. We also observed the concomitant KRAS and BRAF mutation on 5.73% of total CRC cases.…”

Diagnostic Validation of a Clinical Laboratory-Oriented Targeted RNA Sequencing System for Detecting Gene Fusions in Hematologic Malignancies

“…The following quality control parameters and thresholds were used for each step of RNA-seq: RNA integrity number, >7.0 39 ; DV200, !70% 40 ; library fragment size, 270 to 370 bp 41 ; cluster passing filter, !80%; percentage of bases with a quality score !30, !80%; sequencing error rate, <1% 42,43 ; percentage of reads after Q10 trimming, !90%; percentage of uniquely mapped reads, !70%; duplication rate, 70%; on-target rate with !1Â coverage, !90%; and an on-target rate with !100Â coverage, !50%. 39 RNA integrity number DV200 and library fragment size were analyzed using a 4200 TapeStation system (Agilent Technologies).…”