ABSTRACT
BACKGROUND: Squamous cell cancers of the anal canal (ASCC) are increasing in frequency and lack effective therapies for advanced disease. Although an association with human papillomavirus (HPV) has been established, little is known about the molecular characterization of ASCC. A comprehensive genomic analysis of ASCC was undertaken to identify novel genomic alterations (GAs) that will inform therapeutic choices for patients with advanced disease. PATIENTS AND METHODS: Hybrid-capture-based next-generation sequencing of exons from 236 cancer-related genes and intronic regions from 19 genes commonly rearranged in cancer was performed on 70 patients with ASCC. HPV status was assessed by aligning tumor sequencing reads to HPV viral genomes. GAs were identified using an established algorithm and correlated with HPV status. RESULTS: Sixty-one samples (87%) were HPV-positive. A mean of 3.5 GAs per sample was identified. Recurrent alterations in phosphoinositol-3-kinase pathway (PI3K/AKT/mTOR) genes including amplifications and homozygous deletions were present in 63% of cases. Clinically relevant GAs in genes involved in DNA repair, chromatin remodeling, or receptor tyrosine kinase signaling were observed in 30% of cases. Loss-of-function mutations in TP53 and CDKN2A were significantly enhanced in HPV-negative cases (P < 0.0001). CONCLUSIONS: This is the first comprehensive genomic analysis of ASCC, and the results suggest new therapeutic approaches. Differing genomic profiles between HPV-associated and HPV-negative ASCC warrants further investigation and may require novel therapeutic and preventive strategies.
Subject(s)
Anus Neoplasms/genetics , Carcinoma, Squamous Cell/genetics , Cyclin-Dependent Kinase Inhibitor p18/genetics , Genomics , Tumor Suppressor Protein p53/genetics , Adult , Aged , Aged, 80 and over , Anus Neoplasms/pathology , Anus Neoplasms/virology , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/virology , Cyclin-Dependent Kinase Inhibitor p16 , Exons/genetics , Female , High-Throughput Nucleotide Sequencing , Humans , Male , Middle Aged , Mutation , Neoplasm Proteins/genetics , Nuclear Proteins/genetics , Papillomaviridae/genetics , Papillomaviridae/isolation & purification , Papillomaviridae/pathogenicity , Transcription Factors/geneticsSubject(s)
Hypereosinophilic Syndrome/genetics , Oncogene Proteins, Fusion/genetics , Receptor, Platelet-Derived Growth Factor alpha/genetics , Tankyrases/genetics , Benzamides/administration & dosage , Eosinophilia/drug therapy , Eosinophilia/genetics , Eosinophilia/pathology , Female , Genome, Human , High-Throughput Nucleotide Sequencing , Humans , Hypereosinophilic Syndrome/drug therapy , Hypereosinophilic Syndrome/pathology , Imatinib Mesylate , Leukemia , Middle Aged , Myeloproliferative Disorders , Oncogene Proteins, Fusion/isolation & purification , Piperazines/administration & dosage , Pyrimidines/administration & dosageABSTRACT
A case of sporadic dysplastic nevus syndrome is presented, with light and electronic microscopy. The absence of macromelanosomes in the ultrastructural studies of the nevoid lesion supports the nosological identity of the disease (histological marker).
Subject(s)
Melanocytes/ultrastructure , Melanoma/ultrastructure , Neoplasms, Multiple Primary/ultrastructure , Nevus, Pigmented/ultrastructure , Skin Neoplasms/ultrastructure , Adult , False Negative Reactions , Female , Humans , Melanoma/genetics , Neoplasms, Multiple Primary/genetics , Nevus, Pigmented/genetics , Nose Neoplasms/genetics , Nose Neoplasms/ultrastructure , Skin Neoplasms/geneticsABSTRACT
Se comunica un caso de la variedad recidivante de manos y pies de la epidermolisis ampollar simple. Se realiza el estudio con microscopio electronico y se discuten las caracteristicas relevantes de esta enfermedad
Subject(s)
Hand Dermatoses , Foot Dermatoses , Epidermolysis BullosaABSTRACT
Se comunica un caso de la variedad recidivante de manos y pies de la epidermolisis ampollar simple. Se realiza el estudio con microscopio electronico y se discuten las caracteristicas relevantes de esta enfermedad
