Elsevier

Translational Oncology

Volume 23, September 2022, 101471
Translational Oncology

Original Research
Prognosis of ALK-rearranged non-small-cell lung cancer patients carrying TP53 mutations

https://doi.org/10.1016/j.tranon.2022.101471Get rights and content
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Highlights

  • Non-small-cell lung cancer is the primary cause of cancer-related death. TP53 mutations affect patients prognosis, also in oncogene-addicted subgroup. We investigated the role of TP53 mutations in predicting response to therapy and prognosis in ALK-rearranged NSCLC patients, finding that specific TP53 mutations are able to influence patients prognosis.

Abstract

Non-small-cell lung cancer (NSCLC) is the primary cause of cancer-related death. Gene rearrangements involving the anaplastic lymphoma kinase (ALK) tyrosine kinase identify a clinical and molecular subset of NSCLC patients, who benefit from the monotherapy with ALK tyrosine kinase inhibitors. Nonetheless, responsiveness to TKIs and prognosis of these patients are influenced by several factors, including resistance mechanisms and mutations affecting genes involved in key molecular pathways of cancer cells. In a cohort of 98 NSCLC patients with ALK gene rearrangements, we investigated the role of Tumor Protein (TP53) gene mutations in predicting patients prognosis. TP53 mutations were evaluated in relation to disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS) and overall survival (OS).Results: In patients with available clinical and TP53 mutation information, we found that 13 patients (20.3%) were affected by TP53 mutations. Considered together, even though showing a trend, TP53 mutations were not associated with PFS and OS. Considering the different TP53 mutations by functionality in terms of disruptive and non-disruptive mutations, we observed that TP53 non-disruptive mutations were able to predict worse OS in the overall case series. Moreover, a worse PFS was seen in the subgroup of patients with TP53 non-disruptive mutation, in first-, second-, and third line of treatment. Our results show that mutations affecting TP53 gene, especially non-disruptive mutations, are able to affect prognosis of ALK-rearranged NSCLC patients.

Keywords

Non-small cell lung cancer (NSCLC)
Anaplastic lymphoma kinase (ALK) gene re-arrangements
Tumor protein 53 (TP53) gene mutations
Prognosis
Therapy resistance

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