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标题
Heterogeneity of EGFR mutation detected by DHPLC and ARMS
内容
Heterogeneity of EGFR mutation detected by DHPLC and ARMS

Tumor microdissection yielded 2,699 foci, including 1,238 foci from wild-type EGFR (group-W) and 1,431 group-M cases. The overall mutant frequency in group-M was 80.6% by DHPLC (1,154/1,431) and 87.1% (1,247/1,431) by ARMS. Mutant frequencies varied widely throughout individual tumors, ranging between 5%–100% by DHPLC and 1%–100% by ARMS. Group-M samples were subdivided by mutation content as follows: 1) pure EGFR mutation (100%) or no mutational heterogeneity was detected in 21 cases by DHPLC (12 group-M/E19, 9 group-M/E21) and in 31 cases by ARMS (20 group-M/E19, 11 group-M/E21); 2) moderate mutant content (≥50%) or moderate-level heterogeneity was detected in 16 cases by DHPLC (10 group-M/E19, 6 group-M/E21) and in 9 cases by ARMS (2 group-M/E19, 7 group-M/E21); and 3) low mutant content or high-level heterogeneity (<50%) were detected in 8 cases by DHPLC (3 group-M/E19 and 5 group-M/E21) and in 5 cases by ARMS (3 group-M/E19 and 2 group-M/E21).

Among the 40 group-W cases, 4 cases displayed low mutant frequencies ranging from 5.0% to 8.0% when microdissected tumor foci were analyzed by DHPLC. Three of these cases carried an EGFR exon 19 mutation, and one case carried an EGFR exon 21 mutation. ARMS confirmed these 4 cases and identified 6 additional cases showing very low mutant frequencies ranging from 1.0% to 5.0%. By combining the group-M cases carrying both wild- and mutant-type EGFR cells and the group-W cases containing mutant cells at low frequency, 32.9% (28/85) and 28.2% (24/85) of samples were identified to carry intratumoral EGFR mutational heterogeneity by DHPLC and ARMS, respectively. Difference of intratumoral EGFR mutational heterogeneity identified by two methods was not statistical significance (P = 0.031, McNemar's test) (Figure 1).
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来源
PLoS One. 2013; 8(2): e54170.
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