A Sequential Method of Epidermal Growth Factor Receptor Mutation Detection Reduces False Negatives: A New Case With Doublet Mutations of L833V and H835L in China

作者：Zhuang Yuan; Xu Jingjing; Ma Haitao; Zhu Weidong; Guo Linchuan; Kang Suya; Guo Feng^*

来源：Clinical Lung Cancer, 2013, 14(3): 295-300.

DOI：10.1016/j.cllc.2012.11.003

• EGFR mutation
• False-negative
• Workflow for mutation detection

Screening for epidermal growth factor receptor (EGFR) mutation before choosing a therapeutic strategy for patients with advanced non-small-cell lung cancer (NSCLC) is universally accepted at present. One of the reasons that certain patients without activating EGFR mutation respond to EGFR-tyrosine kinase inhibitor (TKI) treatment is possibly due to false-negative EGFR mutation. However, none of the available methods can provide the entire information of EGFR mutation; while maintaining the best sensitivity and specificity. Rare mutations are often evasive due to the limitation of screening methods.
Here, we present a case that can be easily missed due to the chosen method for EGFR mutation detection. The common activating and resistance-related EGFR mutations were all absent from the amplification refractory mutation system assay. Direct DNA sequencing, however, detected complex EGFR mutations of L833V and H835L in EGFR exon 21; therefore, the exact status of EGFR mutation cannot be provided only by a single method.
We report here, to our knowledge, the seventh case in the world and the second case in mainland China of doublet EGFR mutations of L833V and H835L in EGFR exon 21. Albeit rare, this specific type of EGFR mutation deserves more attention because it is related to a good response to EGFR-TKI therapy. To reduce the frequency of false negatives, hence not to lose any opportunities for a potential EGFR-TKI treatment, a sequential workflow by using amplification refractory mutation system assay and/or direct sequencing for EGFR mutation examination according to the specimen quality and quantity (tumor load and DNA yield) is proposed. Clinical Lung Cancer, Vol. 14, No.

• 出版日期2013-5
• 单位苏州大学