Prognostic Significance of Truncating <i>TP53</i> Mutations in Head and Neck Squamous Cell Carcinoma

Plas, Marlon Lindenbergh-van der; Brakenhoff, Ruud H.; Kuik, Dirk J.; Buijze, Marijke; Bloemena, Elisabeth; Snijders, Peter J.F.; Leemans, C. René; Braakhuis, Boudewijn J.M.

doi:10.1158/1078-0432.ccr-11-0183

Cited by 88 publications

(73 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, patients with disruptive mutations showed a significantly shorter OS (2.0 years). These results were confirmed in an independent cohort of patients (45). TP53 disruptive mutations also led to treatment failure through locoregional recurrence in HNSCC (46).…”

Section: Discussionsupporting

confidence: 54%

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

Molina-Vila

Bertrán-Alamillo

Gasco

et al. 2014

Clinical Cancer Research

134

149

View full text Add to dashboard Cite

Purpose: TP53 mutations in early-stage non-small cell lung cancer (NSCLC) may be associated with worse survival but their prognostic role in advanced NSCLC is controversial. In addition, it remains unclear whether mutated patients represent a clinically homogeneous group.Experimental Design: We retrospectively examined TP53 mutations and outcome in a training cohort of 318 patients with stage IIIB-IV NSCLC: 125 epidermal growth factor receptor (EGFR) wild-type (wt) and 193 EGFR mutated (mut). An independent validation cohort of 64 EGFR-mut patients was subsequently analyzed. Mutations were classified as "disruptive" and "nondisruptive" according to their predicted degree of disturbance of the p53 protein structure and function.Results: In the training cohort, TP53 mutations were found in 43 of the 125 EGFR-wt patients (34.4%). Of these, 28 had nondisruptive TP53 mutations and a median overall survival (OS) of 8.5 months, compared with 15.6 months for the remaining 97 patients (P ¼ 0.003). In the EGFR-mut group, TP53 mutations were found in 50 of the 193 patients (25.9%). The OS for the 26 patients with TP53 nondisruptive mutations was 17.8 months versus 28.4 months for the remaining 167 patients (P ¼ 0.04). In the validation cohort, the 11 patients with nondisruptive TP53 mutations had a median OS of 18.1 months compared with 37.8 months for the 53 remaining patients (P ¼ 0.006). In multivariate analyses, nondisruptive TP53 mutations had an independent, significant association with a shorter OS.Conclusions: Nondisruptive mutations in the TP53 gene are an independent prognostic factor of shorter survival in advanced NSCLC.

show abstract

Section: Discussionsupporting

confidence: 54%

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

Molina-Vila

Bertrán-Alamillo

Gasco

et al. 2014

Clinical Cancer Research

134

149

View full text Add to dashboard Cite

show abstract

“…This finding was confirmed in an independent cohort of 141 patients, which reported a TP53 mutation rate of 62.4%. 130 In subgroup analyses, only nonsense mutations that produced a truncated protein were considered s ignificant prognostic factors (HR 2.54, P = 0.008). 130 TP53 mutation is relatively rare in HPV-positive HNSCC.…”

Section: Tp53mentioning

confidence: 99%

Emerging biomarkers in head and neck cancer in the era of genomics

2014

View full text Add to dashboard Cite

Head and neck cancer (HNC) broadly includes carcinomas arising from the mucosal epithelia of the head and neck region as well as various cell types of salivary glands and the thyroid. As reflected by the multiple sites and histologies of HNC, the molecular characteristics and clinical outcomes of this disease vary widely. In this Review, we focus on established and emerging biomarkers that are most relevant to nasopharyngeal carcinoma and head and neck squamous-cell carcinoma (HNSCC), which includes primary sites in the oral cavity, oropharynx, hypopharynx and larynx. Applications and limitations of currently established biomarkers are discussed along with examples of successful biomarker development. For emerging biomarkers, preclinical or retrospective data are also described in the context of recently completed comprehensive molecular analyses of HNSCC, which provide a broad genetic landscape and molecular classification beyond histology and clinical characteristics. We will highlight the ongoing effort that will see a shift from prognostic to predictive biomarker development in HNC with the goal of delivering individualized cancer therapy.

show abstract

“…In addition to tumor initiation, TP53 inactivation also contributes to the clinical behavior of tumors, at least in part independent of an influence on the response to genotoxic therapy. Thus, truncating and functiondisrupting mutations of TP53 are significantly associated with decreased survival -after primary surgery with or without postoperative radiotherapy -compared with either non-disruptive mutations or no mutation at all (22,23).…”

Section: Figurementioning

confidence: 99%