The molecular epidemiology of rare and compound EGFR mutations in 14,304 non-small cell lung carcinomas


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Matthew Evans1,Brendan O'Sullivan1,Frances Hughes1,Claire Swift1,Reena Dessi1,Tina Mullis1,Matthew Smith1,Philippe Taniere1
1Queen Elizabeth Hospital Birmingham

Abstract

Background

The epidemiology of the common Del19 and L858R mutations in non-small cell lung cancer (NSCLC) has been well-characterised. However, few studies have examined the epidemiological characteristics of rarer mutations. We used a large data set from our centre to relate the incidence of these mutations with patient demographics.

Method

All NSCLC cases referred to our centre are tested for EGFR mutations; this is not restricted to adenocarcinoma but also includes NSCLC NOS and tumours showing squamous differentiation. We use real time PCR, using the therascreen EGFR RGQ PCR Kit, which detects exon 19 deletions, T790M, L858R, L861Q, G719X, S768I and exon 20 insertions.

14,304 EGFR mutation results from non-small cell lung cancer specimens tested between 2009 and 2015 were retrospectively reviewed. 1,382 specimens harboured mutations (9.7%), of which 270 contained mutations other than Del19 and L858R. Information was collected about mutation type, patient sex and age.

Results

19.5% of all mutations were rare mutations:

Mutation

G719X

L861Q

S768I

Ins20

T790M

Compound mutations

Incidence

64

4.6%

45

4.7%

14

1.0%

48

3.5%

3

0.2%

76

5.5%

Overall, there was no significant difference in the incidence of rare mutations by sex, and although they were more common with age this did not achieve statistical significance. None of the individual mutations showed a significant difference in incidence by sex. L861Q mutations were significantly more common in older patients, becoming as common as Del19 in patients older than 90 years. T790M, S768I and G719X were markedly overrepresented in the compound mutations.

Conclusion

Rare EGFR mutations are more common than generally assumed, accounting in our series for one fifth of mutations. L861Q is particularly common, being the joint-second commonest mutation in older patient groups. It is therefore important that molecular testing be sensitive to these mutations to avoid denying significant numbers of patients potentially beneficial therapies.

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