Molecular Biology of Head and Neck Cancer: Risks and Pathways

Department of Otolaryngology-Head & Neck Surgery, University of North Carolina at Chapel Hill, CB #7070, Chapel Hill, NC 27599, USA.
Hematology/Oncology Clinics of North America (Impact Factor: 2.3). 01/2009; 22(6):1099-124, vii. DOI: 10.1016/j.hoc.2008.08.007
Source: PubMed


Patients present with a differential baseline risk of cancer based on normal and expected variations in genes associated with cancer. The baseline risk of developing cancer is acted on throughout life as the genome of different cells interacts with the environment in the form of exposures (eg, toxins, infections). As genetic damage is incurred throughout a lifetime (directly to DNA sequences or to the epigenome), events are set in motion to progressively disrupt normal cellular pathways toward tumorigenesis. This article attempts to characterize broad categories of genetic aberrations and pathways in a manner that might be useful for the clinician to understand the risk of developing cancer, the pathways that are disrupted, and the potential for molecular-based diagnostics.

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    • "Molecular tests can provide a better understanding of tumor behavior and improve prognostic predictions, increasing life expectancy in patients with oral SCC to approximately 80% (Forastiere et al., 2001; McCarthy et al., 2004). Disease aggressiveness is directly related to tumor cell adaptation to harsh microenvironment conditions, and the ability to metastasize (Mawrin et al., 2006; Stadler et al., 2008). "
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    ABSTRACT: Death-associated protein 1 (DAP1) is a member of the DAP family. Its expression is associated with cell growth and normal death of the neoplastic cells, regulated by the mammalian target of the rapamycin protein. Activated DAP1 negatively regulates autophagy, which has been associated with the development and progression of several diseases, such as cancer, and with prognosis and survival of diverse tumor types. Therefore, in this study we analyzed DAP1 expression in 54 oral squamous cell carcinoma tumor samples and in 20 non-tumoral margins by immunohistochemistry. The results showed that DAP1 is more frequently expressed in tumor tissues compared with marginal non-tumoral cells. Additionally, high DAP1 expression is associated with a 4-fold increase in the risk of lymph node metastases. Our results suggest that the DAP1 protein can be used as a potential marker of lymph node metastases predisposition, helping define the best therapy for each patient to minimize risk of developing metastases.
    Full-text · Article · Sep 2015 · Genetics and molecular research: GMR
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    • "Head and neck cancer include tumours of the upper aerodigestive tract, parapharyngeal space, paranasal sinuses, thyroid gland, parathyroid gland as well as major and minor salivary glands. Besides these, tumours of the bone and skin present in the head and neck region are also included in head and neck cancer (Stadler et al., 2006). Head and neck cancer (HNNC) is the fifth most common cancer affecting across the globe (Marcu and Yeoh, 2009). "
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    ABSTRACT: Head and neck cancer is included among the top five most commonly prevailing cancers worldwide. Abnormalities of either genetic or epigenetic factors are found responsible for the development and progression of head and neck cancer. Metastasis is the leading cause of death in patients with head and neck cancer. Down regulation of metastasis suppressor genes (MSGs) expression have been frequently observed in advanced tumours. The present study was designed to screen two of the most frequently down-regulated MSGs (KISS1 and KAI1) for mutations in 120 diagnosed head and neck cancer affected Pakistani patients. The questionnaire was filled for basic information about age, gender, smoking habits and area of cancer affected and other relevant details. Primers for both genes were designed using "Primer 3" software in such a way that both intron exon boundaries were included in this region. DNA isolation and estimation was done by using organic method and agarose gel electrophoresis. Single Strand conformational polymorphism technique was used after amplification of the respective genes. Mobility patterns were analyzed using BioDoc Analyzer. Data of patients were analyzed on the basis of age, sex and type of cancer as variables. The mean age of patients and controls was 44 years. There were 53% females and 47% males in this group of study, 63% nonsmokers and 37% smokers and larynx cancer was found to be most frequent type of cancer with a percentage of 64. Lack of germ line mutation was observed in the entire coding region in both coding regions as well as splice sites of the respective genes. Germ line mutations in KISS1 and KAI1 are thus considered to be a less frequent event in head and neck cancer patients. However, two polymorphisms in intronic region of exon 3 and exon 9 of KAI1 gene were observed in 1% of patients. In non coding region downstream of exon 3 (KAI1), there was a C 29166 T substitution and in intronic region upstream exon 9 of KAI1 gene, a C 52840 A substitution was observed. Both patients were females with ages 47 and 50 years respectively. A detailed analysis of regulatory mechanism is required to explore the genetic basis of down regulation of these MSGs for a better understanding of head and neck cancer progression.
    Full-text · Article · Jan 2011 · Asian Pacific journal of cancer prevention: APJCP
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    • "The moderate staining of keratin found in the heterotransplant tumor sections is similar with the original tumor, described as a keratinizing squamous cell carcinoma. The light staining of E-cadherin in the heterotransplanted tumor may indicate the malignant potential of the cells as they begin to undergo epithelial-to-mesenchymal transition and consequently lose cell-cell adhesive and interactive molecules [12,19]. When the malignant cells are placed in a murine host, they are subjected to a myriad of microenvironmental factors different from that of cell culture medium or a human host. "
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    ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) is an aggressive and lethal malignancy. Publically available cell lines are mostly of lingual origin, or have not been carefully characterized. Detailed characterization of novel HNSCC cell lines is needed in order to provide researchers a concrete keystone on which to build their investigations. The USC-HN1 cell line was established from a primary maxillary HNSCC biopsy explant in tissue culture. The immortalized cells were then further characterized by heterotransplantation in Nude mice; immunohistochemical staining for relevant HNSCC biomarkers; flow cytometry for surface markers; cytogenetic karyotypic analysis; human papillomavirus and Epstein-Barr virus screening; qRT-PCR for oncogene and cytokine analysis; investigation of activated, cleaved Notch1 levels; and detailed 35,000 gene microarray analysis. Characterization experiments confirmed the human HNSCC origin of USC-HN1, including a phenotype similar to the original tumor. Viral screening revealed no HPV or EBV infection, while western blotting displayed significant upregulation of activated, cleaved Notch1. USC-HN1, a novel immortalized cell line has been derived from a maxillary HNSCC. Characterization studies have shown that the cell line is of HNSCC origin and displays many of the same markers previously reported in the literature. USC-HN1 is available for public research and will further the investigation of HNSCC and the development of new therapeutic modalities.
    Full-text · Article · Feb 2010 · Head & Neck Oncology
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