Nondisruptive p53 Mutations Are Associated with Shorter Survival in Patients with Advanced Non–Small Cell Lung Cancer

Molina-Vila, Miguel Ángel; Bertrán-Alamillo, Jordi; Gasco, Amaya; Mayo‐de‐las‐Casas, Clara; Sanchez-Ronco, María; Pujantell-Pastor, Laia; Bonanno, Laura; Favaretto, Adolfo; Cardona, Andrés Felipe; Vergnenègre, A.; Majem, Margarita; Massutí, Bartomeu; Morán, Teresa; Carcereny, Enric; Viteri, Santiago; Rosell, Rafael

doi:10.1158/1078-0432.ccr-13-2391

Cited by 138 publications

(173 citation statements)

References 45 publications

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“…In breast cancer, for example, it is well established that missense mutations affecting DNA binding are associated with worse patient survival than missense mutations outside of DNA-binding motifs (Olivier et al 2006). It has since become apparent that the specific functional properties of p53 mutant proteins play a key role in conferring several tumor types with poor prognosis and therapeutic resistance (Poeta et al 2007;Govindan and Weber 2014;Molina-Vila et al 2014;Brachova et al 2015). Crystallographic studies focused on the interaction of p53 and its cancer-associated mutants with DNA have led to a classification system that defines mutations occurring in the p53-DNA-binding surface as contact mutations Mutations are classified as substitution, deletion, insertion, or complex mutations.…”

Section: Functional Classification Of Tp53 Mutations and Their Clinicmentioning

confidence: 99%

Clinical Outcomes of TP53 Mutations in Cancers

Robles

Jen

Harris

2016

Cold Spring Harb Perspect Med

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High-throughput sequencing of cancer genomes is increasingly becoming an essential tool of clinical oncology that facilitates target identification and targeted therapy within the context of precision medicine. The cumulative profiles of somatic mutations in cancer yielded by comprehensive molecular studies also constitute a fingerprint of historical exposures to exogenous and endogenous mutagens, providing insight into cancer evolution and etiology. Mutational signatures that were first established by inspection of the TP53 gene somatic landscape have now been confirmed and expanded by comprehensive sequencing studies. Further, the degree of granularity achieved by deep sequencing allows detection of low-abundance mutations with clinical relevance. In tumors, they represent the emergence of small aggressive clones; in normal tissues, they signal a mutagenic exposure related to cancer risk; and, in blood, they may soon become effective surveillance tools for diagnostic purposes and for monitoring of cancer prognosis and recurrence.

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Section: Functional Classification Of Tp53 Mutations and Their Clinicmentioning

confidence: 99%

Clinical Outcomes of TP53 Mutations in Cancers

Robles

Jen

Harris

2016

Cold Spring Harb Perspect Med

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“…At least in NSCLC, the prognostic role of the TP53 gene is controversial and not all mutated patients represent a clinically homogeneous group (11). We have found that "nondisruptive" TP53 mutations, may apparently confer oncogenic activities to the mutated p53 protein, and define a group of metastatic NSCLC patients with a dismal prognosis (11). In contrast, patients with 'disruptive' TP53 mutations characterized by a complete, or almost complete, loss of activity of the p53 protein, have good prognosis, similar to patients with wild-type TP53 (11).…”

mentioning

confidence: 93%

“…We have found that "nondisruptive" TP53 mutations, may apparently confer oncogenic activities to the mutated p53 protein, and define a group of metastatic NSCLC patients with a dismal prognosis (11). In contrast, patients with 'disruptive' TP53 mutations characterized by a complete, or almost complete, loss of activity of the p53 protein, have good prognosis, similar to patients with wild-type TP53 (11). In the study of Dowlati et al, SCLC patients with 'disruptive' TP53 mutations had a significantly better response to first-line chemotherapy compared to patients with wild-type TP53.…”

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confidence: 99%

Unraveling the genomic complexity of small cell lung cancer

Karachaliou¹,

Sosa²,

Rosell³

2016

Transl. Lung Cancer Res.

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“…In addition, no significant correlation was observed between the expression of p53 and PFS. A previous study reported that non-disruptive mutations in the TP53 gene are an independent prognostic factor of shorter survival rates in advanced NSCLC (37), whereas another study showed that p53 mutations are significantly correlated with tumor relapse in patients with stage I disease (38). The tumor suppressor gene, TP53, is the most frequently mutated gene in NSCLC (39).…”

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confidence: 99%

Correlation between epidermal growth factor receptor mutations and the expression of estrogen receptor-β in advanced non-small cell lung cancer

Deng

Shan

et al. 2017

Oncology Letters

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Abstract. Epidermal growth factor receptor (EGFR) mutations are more common in non-small cell lung cancer (NSCLC) and in female patients of East Asian origin. Therefore, the present study investigated the presence of EGFR mutations in advanced NSCLC, and assessed its correlation with clinicopathologic factors, including the expression of estrogen receptor-β (ER-β) and patient prognosis. The present study performed a retrospective analysis of 83 patients with stage IIIB-IV NSCLC. The expression of ER-β and p53 were examined using immunohistochemical methods. EGFR mutations were evaluated using the amplification refractory mutation system. The expression of ER-β and p53 were detected in 37 (45.6%) and 48 (57.8%) of the patient tumors, respectively. EGFR mutations were identified in 36 (45.4%) cases. EGFR mutations were more frequently observed in ER-β-negative tumors (26/46; 56.5%), compared with ER-β-positive tumors (10/37; 27%). The expression of ER-β was significantly associated with EGFR mutations with an odds ratio (OR) of 0.241 (P=0.029). However, no significant correlation was observed between the expression of p53 and mutations in EGFR (OR=1.792; P=0.340). In addition, the expression of ER-β and lymph node metastasis were associated with poor prognosis, whereas EGFR mutations were significantly associated with favorable prognosis in terms of progression-free survival rates. However, there was no prognostic significance associated with the expression of p53. In conclusion, the expression of ER-β was significantly correlated with the presence of EGFR mutations. The expression of ER-β and mutations of EGFR were found to be prognostic factors for survival rates in patients with advanced NSCLC.

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Nondisruptive p53 Mutations Are Associated with Shorter Survival in Patients with Advanced Non–Small Cell Lung Cancer

Cited by 138 publications

References 45 publications

Clinical Outcomes of TP53 Mutations in Cancers

Clinical Outcomes of TP53 Mutations in Cancers

Unraveling the genomic complexity of small cell lung cancer

Correlation between epidermal growth factor receptor mutations and the expression of estrogen receptor-β in advanced non-small cell lung cancer

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