Dataset Information

TP53 Loss of Heterozygosity Induces De Novo SCLC Formation in EGFR-Mutated Lung Adenocarcinoma: A Case Report.

ABSTRACT: SCLC transformation in EGFR-mutated lung adenocarcinoma is one of the major phenotypic changes that is observed during the resistance to EGFR tyrosine kinase inhibitors. However, the mechanism of this transformation remains unclear. In this study, we found a small de novo SCLC component in surgically resected specimens of EGFR-mutated lung adenocarcinoma before EGFR tyrosine kinase inhibitor treatment. By using laser microdissection and whole-exome sequencing, TP53 loss of heterozygosity was found to be possibly involved in SCLC transformation.

SUBMITTER: Kunimasa K

PROVIDER: S-EPMC9052150 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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<i>TP53</i> Loss of Heterozygosity Induces De Novo SCLC Formation in EGFR-Mutated Lung Adenocarcinoma: A Case Report.

Kunimasa Kei K Hirotsu Yosuke Y Amemiya Kenji K Nakamura Harumi H Nishino Kazumi K Honma Keiichiro K Okami Jiro J Omata Masao M Kumagai Toru T

JTO clinical and research reports 20220319 5

SCLC transformation in EGFR-mutated lung adenocarcinoma is one of the major phenotypic changes that is observed during the resistance to EGFR tyrosine kinase inhibitors. However, the mechanism of this transformation remains unclear. In this study, we found a small de novo SCLC component in surgically resected specimens of EGFR-mutated lung adenocarcinoma before EGFR tyrosine kinase inhibitor treatment. By using laser microdissection and whole-exome sequencing, <i>TP53</i> loss of heterozygosity ...[more]

PMID: 35498386

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Project description:BackgroundMetastatic epidermal growth factor receptor-mutated (EGFR+) non-small-cell lung cancer (NSCLC) can present de novo or following previous nonmetastatic disease (secondary). Potential differences between these two patient subsets are unclear at present.MethodsWe retrospectively analyzed characteristics of tyrosine kinase inhibitor (TKI)-treated patients with de novo vs. secondary metastatic EGFR+ NSCLC until December 2019 (n = 401).ResultsDe novo metastatic disease was 4× more frequent than secondary (n = 83/401), but no significant differences were noted regarding age (median 66 vs. 70 years), sex (65% vs. 65% females), smoking history (67% vs. 62% never/light-smokers), and histology (both >95% adenocarcinoma). Patients with secondary metastatic disease showed a better ECOG performance status (PS 0-1 67%-32% vs. 46%-52%, p = 0.003), fewer metastatic sites (mean 1.3 vs. 2.0, p < 0.001), and less frequent brain involvement (16% vs. 28%, p = 0.022) at the time of stage IV diagnosis. Progression-free survival (PFS) under TKI (median 17 for secondary vs. 12 months for de novo, p = 0.26) and overall survival (OS, 29 vs. 25 months, respectively, p = 0.47) were comparable. EGFR alterations (55% vs. 60% exon 19 deletions), TP53 mutation rate at baseline (47% vs. 43%, n = 262), and T790M positivity at the time of TKI failure (51% vs. 56%, n = 193) were also similar. OS according to differing characteristics, e.g., presence or absence of brain metastases (19-20 or 30-31 months, respectively, p = 0.001), and ECOG PS 0 or 1 or 2 (32-34 or 20-23 or 5-7 months, respectively, p < 0.001), were almost identical for de novo and secondary metastatic disease.ConclusionsDespite the survival advantage reported in the pre-TKI era for relapsed NSCLC, molecular features and outcome of TKI-treated metastatic EGFR+ tumors are currently independent of preceding nonmetastatic disease. This simplifies design of outcome studies and can assist prognostic considerations in everyday management of patients with secondary metastatic EGFR+ tumors.

Dataset Information

TP53 Loss of Heterozygosity Induces De Novo SCLC Formation in EGFR-Mutated Lung Adenocarcinoma: A Case Report.

Publications

<i>TP53</i> Loss of Heterozygosity Induces De Novo SCLC Formation in EGFR-Mutated Lung Adenocarcinoma: A Case Report.

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