Dataset Information

Classification of TP53 mutations and HPV predict survival in advanced larynx cancer.

ABSTRACT: Assess tumor suppressor p53 (TP53) functional mutations in the context of other biomarkers in advanced larynx cancer.Prospective analysis of pretreatment tumor TP53, human papillomavirus (HPV), Bcl-xL, and cyclin D1 status in stage III and IV larynx cancer patients in a clinical trial.TP53 exons 4 through 9 from 58 tumors were sequenced. Mutations were grouped using three classifications based on their expected function. Each functional group was analyzed for response to induction chemotherapy, time to surgery, survival, HPV status, p16INK4a, Bcl-xl, and cyclin D1 expression.TP53 mutations were found in 22 of 58 (37.9%) patients with advanced larynx cancer, including missense mutations in 13 of 58 (22.4%) patients, nonsense mutations in four of 58 (6.9%), and deletions in five of 58 (8.6%). High-risk HPV was found in 20 of 52 (38.5%) tumors. A classification based on Evolutionary Action score of p53 (EAp53) distinguished missense mutations with high risk for decreased survival from low-risk mutations (P = 0.0315). A model including this TP53 classification, HPV status, cyclin D1, and Bcl-xL staining significantly predicts survival (P = 0.0017).EAp53 functional classification of TP53 mutants and biomarkers predict survival in advanced larynx cancer.NA. Laryngoscope, 126:E292-E299, 2016.

SUBMITTER: Scheel A

PROVIDER: S-EPMC5002993 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Classification of TP53 mutations and HPV predict survival in advanced larynx cancer.

Scheel Adam A Bellile Emily E McHugh Jonathan B JB Walline Heather M HM Prince Mark E ME Urba Susan S Wolf Gregory T GT Eisbruch Avraham A Worden Francis F Carey Thomas E TE Bradford Carol C

The Laryngoscope 20160627 9

<h4>Objectives/hypothesis</h4>Assess tumor suppressor p53 (TP53) functional mutations in the context of other biomarkers in advanced larynx cancer.<h4>Study design</h4>Prospective analysis of pretreatment tumor TP53, human papillomavirus (HPV), Bcl-xL, and cyclin D1 status in stage III and IV larynx cancer patients in a clinical trial.<h4>Methods</h4>TP53 exons 4 through 9 from 58 tumors were sequenced. Mutations were grouped using three classifications based on their expected function. Each fun ...[more]

PMID: 27345657

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Project description:BackgroundNon-melanoma skin cancers are one of the most common human malignancies accounting for 2-3% of tumors in the US and represent a significant health burden. Epidemiology studies have implicated Tp53 mutations triggered by UV exposure, and human papilloma virus (HPV) infection to be significant causes of non-melanoma skin cancer. However, the relationship between Tp53 and cutaneous HPV infection is not well understood in skin cancers. In this study we assessed the association of HPV infection and Tp53 polymorphisms and mutations in lesional specimens with squamous cell carcinomas.MethodsWe studied 55 cases of histologically confirmed cutaneous squamous cell carcinoma and 41 controls for the presence of HPV infection and Tp53 genotype (mutations and polymorphism).ResultsWe found an increased number of Tp53 mutations in the squamous cell carcinoma samples compared with perilesional or control samples. There was increased frequency of homozygous Tp53-72R polymorphism in cases with squamous cell carcinomas, while the Tp53-72P allele (Tp53-72R/P and Tp53-72P/P) was more frequent in normal control samples. Carcinoma samples positive for HPV showed a decreased frequency of Tp53 mutations compared to those without HPV infection. In addition, carcinoma samples with a Tp53-72P allele showed an increased incidence of Tp53 mutations in comparison carcinomas samples homozygous for Tp53-72R.ConclusionsThese studies suggest there are two separate pathways (HPV infection and Tp53 mutation) leading to cutaneous squamous cell carcinomas stratified by the Tp53 codon-72 polymorphism. The presence of a Tp53-72P allele is protective against cutaneous squamous cell carcinoma, and carcinoma specimens with Tp53-72P are more likely to have Tp53 mutations. In contrast Tp53-72R is a significant risk factor for cutaneous squamous cell carcinoma and is frequently associated with HPV infection instead of Tp53 mutations. Heterozygosity for Tp53-72R/P is protective against squamous cell carcinomas, possibly reflecting a requirement for both HPV infection and Tp53 mutations.

Dataset Information

Classification of TP53 mutations and HPV predict survival in advanced larynx cancer.

Publications

Classification of TP53 mutations and HPV predict survival in advanced larynx cancer.

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