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The Presence of EGFR T790M in TKI-Naïve Lung Cancer Samples of Patients Who Developed a T790M-Positive Relapse on First or Second Generation TKI Is Rare
| Content Provider | MDPI |
|---|---|
| Author | Li, Weiting Kok, Klaas Tan, Geok Wee Meng, Pei Mastik, Mirjam Rifaela, Naomi Scherpen, Frank Hiltermann, T. Jeroen N. Groen, Harry J. M. van der Wekken, Anthonie J. Berg, Anke Van Den |
| Copyright Year | 2022 |
| Description | EGFR-mutated non-small cell lung cancer (NSCLC) patients can be effectively treated with tyrosine kinase inhibitors (TKI) but frequently present with an EGFR T790M resistance mutation at relapse. We aimed to screen for T790M in pre-treatment formalin-fixed and paraffin-embedded (FFPE) tissue samples of patients with a confirmed T790M mutation at progression. We analyzed 33 pre-treatment DNA samples of NSCLC patients who progressed upon TKI between 2013 to 2019. To establish storage-time dependent formalin fixation-induced background levels for C>T mutations, we analyzed DNA isolated from archival (stored >1 year, n = 22) and recently generated (stored <1 month, n = 11) FFPE samples and included DNA isolated from white blood cells (WBC) (n = 24) as controls. DNA samples were analyzed by droplet digital (dd)PCR, and positivity was defined by outlier detection according to Grubb’s criterion. The T790M background allele frequency levels were 0.160% in DNA isolated from archival-FFPE, 0.100% in fresh FFPE, and 0.035% in WBC. Progression-free survival (PFS) time of the single T790M positive patient was 9 months, while T790M negative patients had a median PFS of 10 months (range 2–27). Proper storage time matched FFPE control samples are essential for reliable detection of T790M mutation at low VAF. The presence of EGFR T790M mutations in pre-TKI samples is rare, even in patients who progressed with EGFR T790M mutations. |
| Starting Page | 3511 |
| e-ISSN | 20726694 |
| DOI | 10.3390/cancers14143511 |
| Journal | Cancers |
| Issue Number | 14 |
| Volume Number | 14 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2022-07-19 |
| Access Restriction | Open |
| Subject Keyword | Cancers Oncology Nsclc Egfr Tki T790m Ddpcr |
| Content Type | Text |
| Resource Type | Article |
