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- Title
Degraded DNA may induce discordance of KRAS status between primary colorectal cancer and corresponding liver metastases.
- Authors
Kaneko, Yuka; Kuramochi, Hidekazu; Nakajima, Go; Inoue, Yuji; Yamamoto, Masakazu
- Abstract
Background: KRAS mutation is widely accepted as a strong, negative predictive marker for anti-epidermal growth factor receptor antibodies, including cetuximab and panitumumab. Previous reports demonstrated approximately 100 % concordance of KRAS status between primary colorectal cancer and liver metastases; however, mismatched KRAS status still occurs. Methods: KRAS status was evaluated in 105 pairs of formalin-fixed primary colorectal cancer and corresponding liver metastases specimens by direct sequencing. DNA quality of patients displaying mismatched KRAS status between primary tumors and metastases was assessed using a Bioanalyzer. Results: KRAS status was successfully analyzed in 90/105 patients (85.7 %). The concordance rate between primary tumors and metastases was 88.2 % in synchronous metastases ( n = 76) and 100 % in metachronous metastases ( n = 14). Discordance in KRAS status was observed in nine patients. Independent method validation revealed only five samples showed the same KRAS status between the two methods. DNA quality assessment by a Bioanalyzer revealed that the median length of DNA samples in the peak concentration of the mismatched group was significantly shorter than those in the control group (153.5 vs 276.5 bp, P = 0.0059). In addition, the median value of the percentage of degraded DNA (0-200 bp) in each sample in the mismatched group was significantly higher than the control group (35.5 vs 22 %, P = 0.020). These data suggest that the discordant results for these nine patients (18 samples) were due to low quality DNA, which may obscure polymerase chain reaction analysis, affecting sequencing reliability. Conclusion: Quality control and assurance of KRAS genotyping is critical, and standardization of the methodology is warranted.
- Subjects
COLON cancer; LIVER metastasis; GENETIC mutation; EPIDERMAL growth factor receptors regulation; IMMUNOGLOBULINS; CETUXIMAB; MEDICAL quality control
- Publication
International Journal of Clinical Oncology, 2014, Vol 19, Issue 1, p113
- ISSN
1341-9625
- Publication type
Article
- DOI
10.1007/s10147-012-0507-4