CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Conclusion. The combination of two genomic aberrations of the EGFR gene—exon 19 deletion and primary p.T790M mutation—was responsive to the third-generation EGFR TKI inhibitor osimertinib, with minimal adverse effects, in this patient with metastatic lung adenocarcinoma.
- Yu HA, Arcila ME, Hellmann MD, Kris MG, Ladanyi M, Riely GJ. Poor response to erlotinib in patients with tumors containing baseline EGFR T790M mutations found by routine clinical molecular testing. Ann Oncol. 2014;25(2):423–428.
- Su KY, Chen HY, Li KC, et al. Pretreatment epidermal growth factor receptor (EGFR) T790M mutation predicts shorter EGFR tyrosine kinase inhibitor response duration in patients with non-small-cell lung cancer. J Clin Oncol. 2012;30(4):433–440.
- Riely GJ, Yu HA, Arcila ME, Hellmann MD, Ladanyi M, Kris MG. Response to erlotinib and prognosis for patients with de novo epidermal growth factor receptor (EGFR) T790M mutations. J Clin Oncol. 2013;31(15)(suppl):8018.
- Pao W, Miller V, Zakowski M, et al. EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci USA. 2004;101(36):13306–13311.
- Hata A, Yoshioka H, Fujita S, et al. Complex mutations in the epidermal growth factor receptor gene in non-small cell lung cancer. J Thorac Oncol. 2010;5(10):1524–1528.
- Zhang B, Xu J, Zhang X, et al. Coexistence of sensitive and resistant epidermal growth factor receptor (EGFR) mutations in pretreatment non-small cell lung cancer (NSCLC) patients: first or third generation tyrosine kinase inhibitors (TKIs)? Lung Cancer. 2018;117:27–31.
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Drs. Limaye, Pusalkar, Kothari, Hastak, Vadera, Mistry, and Vyas are with Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai, India.
Test yourself
- Here are three questions taken from the case report.
- Answers
1. The p.T790M mutation in EGFR is clinically significant because:
a. Its detection means increased sensitivity to tyrosine kinase inhibitors.
b. It arises as a secondary resistance mutation in response to first-generation tyrosine kinase inhibitors.
c. Patients with this mutation respond well to osimertinib.
2. Presence of a compound mutation in the EGFR gene:
a. means there are two or more different heterozygous mutations present in the same gene.
b. complicates and alters the patient’s response to targeted therapy.
c. means real-time PCR will be a good technique for detection.
3. Which technique is ideal to detect all possible EGFR mutations present in a patient’s sample?
a. Sanger sequencing.
b. Real-time PCR—it is a sensitive technique and can detect mutations in samples with low tumor content.
c. Next-generation sequencing—it is a sensitive tool to detect rare and common EGFR mutations.
a. Its detection means increased sensitivity to tyrosine kinase inhibitors.
b. It arises as a secondary resistance mutation in response to first-generation tyrosine kinase inhibitors.
c. Patients with this mutation respond well to osimertinib.
2. Presence of a compound mutation in the EGFR gene:
a. means there are two or more different heterozygous mutations present in the same gene.
b. complicates and alters the patient’s response to targeted therapy.
c. means real-time PCR will be a good technique for detection.
3. Which technique is ideal to detect all possible EGFR mutations present in a patient’s sample?
a. Sanger sequencing.
b. Real-time PCR—it is a sensitive technique and can detect mutations in samples with low tumor content.
c. Next-generation sequencing—it is a sensitive tool to detect rare and common EGFR mutations.