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Updated: Mar 15, 2026
Detection of Rare Mutations in CtDNA Using Next Generation Sequencing
Published on: August 24, 2017
Targeted molecular profiling of rare genetic alterations in colorectal cancer using next-generation sequencing
Mayank Jauhri1, Akanksha Bhatnagar2, Satish Gupta3
1Department of Medical Oncology, Sir Ganga Ram Hospital, New Delhi, 110060, India. mayank.jauhri@yahoo.com.
Abstract:
Mutation frequencies of common genetic alterations in colorectal cancer have been in the spotlight for many years. This study highlights few rare somatic mutations, which possess the attributes of a potential CRC biomarker yet are often neglected. Next-generation sequencing was performed over 112 tumor samples to detect genetic alterations in 31 rare genes in colorectal cancer. Mutations were detected in 26/31 (83.9 %) uncommon genes, which together contributed toward 149 gene mutations in 67/112 (59.8 %) colorectal cancer patients. The most frequent mutations include KDR (19.6 %), PTEN (17 %), FBXW7 (10.7 %), SMAD4 (10.7 %), VHL (8 %), KIT (8 %), MET (7.1 %), ATM (6.3 %), CTNNB1 (4.5 %) and CDKN2A (4.5 %). RB1, ERBB4 and ERBB2 mutations were persistent in 3.6 % patients. GNAS, FGFR2 and FGFR3 mutations were persistent in 1.8 % patients. Ten genes (EGFR, NOTCH1, SMARCB1, ABL1, STK11, SMO, RET, GNAQ, CSF1R and FLT3) were found mutated in 0.9 % patients. Lastly, no mutations were observed in AKT, HRAS, MAP2K1, PDGFR and JAK2. Significant associations were observed between VHL with tumor site, ERBB4 and SMARCB1 with tumor invasion, CTNNB1 with lack of lymph node involvement and CTNNB1, FGFR2 and FGFR3 with TNM stage. Significantly coinciding mutation pairs include PTEN and SMAD4, PTEN and KDR, EGFR and RET, EGFR and RB1, FBXW7 and CTNNB1, KDR and FGFR2, FLT3 and CTNNB1, RET and RB1, ATM and SMAD4, ATM and CDKN2A, ERBB4 and SMARCB1. This study elucidates few potential colorectal cancer biomarkers, specifically KDR, PTEN, FBXW7 and SMAD4, which are found mutated in more than 10 % patients.
Insights
This study identifies rare somatic mutations in colorectal cancer (CRC) as potential biomarkers. Key genes like KDR, PTEN, FBXW7, and SMAD4 show frequent mutations, offering new diagnostic avenues for CRC.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Common genetic alterations in colorectal cancer (CRC) are well-studied.
- Rare somatic mutations in CRC often present as potential biomarkers but are frequently overlooked.
Purpose of the Study:
- To identify and analyze rare somatic mutations in 31 specific genes within 112 colorectal cancer tumor samples.
- To evaluate the potential of these rare mutations as biomarkers for colorectal cancer.
Main Methods:
- Next-generation sequencing (NGS) was employed to analyze genetic alterations in 112 colorectal cancer tumor samples.
- The study focused on detecting mutations in 31 less common genes associated with CRC.
Main Results:
- Mutations were detected in 83.9% of the analyzed uncommon genes, present in 59.8% of patients.
- Frequent mutations were observed in KDR (19.6%), PTEN (17%), FBXW7 (10.7%), and SMAD4 (10.7%).
- Significant associations were found between specific mutations (VHL, ERBB4, SMARCB1, CTNNB1, FGFR2, FGFR3) and clinicopathological features like tumor site, invasion, lymph node involvement, and TNM stage.
Conclusions:
- Rare mutations in genes such as KDR, PTEN, FBXW7, and SMAD4 are prevalent in colorectal cancer and represent promising biomarkers.
- The study highlights the importance of investigating less common genetic alterations for improved CRC diagnostics and understanding.
