Degraded DNA may induce discordance of KRAS status between primary colorectal cancer and corresponding liver metastases

作者：Kaneko Yuka; Kuramochi Hidekazu^*; Nakajima Go; Inoue Yuji; Yamamoto Masakazu

来源：International Journal of Clinical Oncology, 2014, 19(1): 113-120.

DOI：10.1007/s10147-012-0507-4

• KRAS
• Mutation
• Liver metastases
• Bioanalyzer

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. %26lt;br%26gt;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. %26lt;br%26gt;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. %26lt;br%26gt;Conclusion Quality control and assurance of KRAS genotyping is critical, and standardization of the methodology is warranted.

• 出版日期2014-2