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Cancers 2019, 11(1), 124; https://doi.org/10.3390/cancers11010124

Detection of TP53 Mutations in Tissue or Liquid Rebiopsies at Progression Identifies ALK+ Lung Cancer Patients with Poor Survival

1
Department of Thoracic Oncology, Heidelberg University Hospital, 69126 Heidelberg, Germany
2
Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), 69120 Heidelberg, Germany
3
Division of Cancer Genome Research, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany
4
German Cancer Consortium (DKTK), 69120 Heidelberg, Germany
5
Institute of Pathology, Heidelberg University Hospital, 69120 Heidelberg, Germany
6
Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik at Heidelberg University Hospital, 69126 Heidelberg, Germany
7
Department of Diagnostic and Interventional Radiology, Heidelberg University Hospital, 69120 Heidelberg, Germany
8
Department of Pneumology, Thoraxklinik at Heidelberg University Hospital, 69126 Heidelberg, Germany
9
Department of Surgery, Thoraxklinik at Heidelberg University Hospital, 69126 Heidelberg, Germany
10
Translational Research Unit, Thoraxklinik at Heidelberg University Hospital, 69126 Heidelberg, Germany
11
BIH-Genomics Core Unit, Charité-Universitätsmedizin Berlin, 13125 Berlin, Germany
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 10 December 2018 / Revised: 15 January 2019 / Accepted: 18 January 2019 / Published: 21 January 2019
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Abstract

Anaplastic lymphoma kinase (ALK) sequencing can identify resistance mechanisms and guide next-line therapy in ALK+ non-small-cell lung cancer (NSCLC), but the clinical significance of other rebiopsy findings remains unclear. We analysed all stage-IV ALK+ NSCLC patients with longitudinally assessable TP53 status treated in our institutions (n = 62). Patients with TP53 mutations at baseline (TP53mutbas, n = 23) had worse overall survival (OS) than patients with initially wild-type tumours (TP53wtbas, n = 39, 44 vs. 62 months in median, p = 0.018). Within the generally favourable TP53wtbas group, detection of TP53 mutations at progression defined a “converted” subgroup (TP53mutconv, n = 9) with inferior OS, similar to that of TP53mutbas and shorter than that of patients remaining TP53 wild-type (TP53wtprogr, 45 vs. 94 months, p = 0.043). Progression-free survival (PFS) under treatment with tyrosine kinase inhibitors (TKI) for TP53mutconv was comparable to that of TP53mutbas and also shorter than that of TP53wtprogr cases (5 and 8 vs. 13 months, p = 0.0039). Fewer TP53wtprogr than TP53mutbas or TP53mutconv cases presented with metastatic disease at diagnosis (67% vs. 91% or 100%, p < 0.05). Thus, acquisition of TP53 mutations at progression is associated with more aggressive disease, shorter TKI responses and inferior OS in ALK+ NSCLC, comparable to primary TP53 mutated cases. View Full-Text
Keywords: anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC); tumor protein p53 gene (TP53) mutation; tyrosine kinase inhibitor; progression-free survival; overall survival anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC); tumor protein p53 gene (TP53) mutation; tyrosine kinase inhibitor; progression-free survival; overall survival
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Christopoulos, P.; Dietz, S.; Kirchner, M.; Volckmar, A.-L.; Endris, V.; Neumann, O.; Ogrodnik, S.; Heussel, C.-P.; Herth, F.J.; Eichhorn, M.; Meister, M.; Budczies, J.; Allgäuer, M.; Leichsenring, J.; Zemojtel, T.; Bischoff, H.; Schirmacher, P.; Thomas, M.; Sültmann, H.; Stenzinger, A. Detection of TP53 Mutations in Tissue or Liquid Rebiopsies at Progression Identifies ALK+ Lung Cancer Patients with Poor Survival. Cancers 2019, 11, 124.

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