01132 - Molecular Pathology - Immunology (Integrated Course) (AK-C)

Learning outcomes

At the end of the course the student knows the mechanism through which genomic alterations cause diseases; the phenotype of tumor cells, the origin and natural history of tumors within the framework of cancer prevention and innovative preclinical approaches to the control of cancer; the student is able to apply this knowledge to specific pathologies.

Course contents

The course of Molecular Pathology is comprised of a "Genetic Pathology" part (2 credits, prof. Lollini) and an Oncology part (3 credits, Prof. Lollini and Nanni). The following syllabus includes both parts.

GENETIC PATHOLOGY

Mutations: types and causes and their pathogenetic effects. Outlines on multifactorial and mithochondrial diseases. DNA damage repair mechanisms: NER, BER, non homologous end joining (NHEJ), homologous recombination and mismatch repair. The network of genotoxic damage detection. Chromosomal disorders: Del22q11 syndrome. Mendelian disorders. Alterations of cytoskeleton proteins: Duchenne and Becker dystrophies. Alterations of extracellular matrix proteins: collagen diseases (osteogenesis imperfecta). Alterations of lysosomal enzymes: The Tay-Sachs disease. Alterations of ion channels: cystic fibrosis. Epigenetic and postranscriptional mechanisms of control of gene expression: Genomic imprinting: the Prader-Willi and Angelman syndromes. Disease caused by trinucleotide repeat expansions: fragile-X syndrome Huntington corea and locus C9orf72. Molecular techniques: polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH). Expression and genomic microarray techniques. CRISPR/Cas9. Next Generation Sequencing (NGS). Hereditary cancer syndromes: “gatekeeper” genes: retinoblastoma and the Knudson's hypothesis. Role of Rb protein. Familial adenomatous polyposis: the role of APC protein in the cell cycle control. The concept of loss of heterozygosis (LOH). The von Hippel Lindau syndrome and the hypoxia responsive mechanisms. gastric cancer and E-cadherin. “Caretaker” genes. Role of ATM and p53 genes. Alterations of gatekeeper genes. Xeroderma pigmentosum, ataxia telangiectasia, hereditary breast cancer, Li-Fraumeni syndrome, non-polyposis colorectal cancer. Alterations of microsatellite sequences. Multiple endocrine neoplasia (MEN).

ONCOLOGY

Introduction, definitions and classification. Basic Oncology and Medical Oncology. The size of the problem. Benign and malignant tumors. Tumors are genic diseases. Oncogenes and tumor suppressor genes, "gatekeepers" and "caretakers". Mechanisms of cancer gene activation/inactivation and their consequences. Therapeutic implications of oncogenes and tumor suppressor genes. Genetic predispositions. The neoplastic phenotype. Growth, Differentiation, Cell death. Genomic instability. Morphological and metabolic features. Natural history. Monoclonality, Heterogeneity. Preneoplastic lesions. Progression. The causes of cancer. Exogenous and endogenous carcinogens. Biological and molecular mechanisms of physical, chemical and biological carcinogenesis. Cancer epidemiology. Primary, secondary and tertiary cancer prevention. Chemoprevention. Immunoprevention. Tumor-host relationships. Angiogenesis. The metastatic process. Paraneoplastic syndromes. Tumor immunology. Fundamentals of cancer therapy. Basis and molecular/biological mechanisms of cancer therapy: radiation therapy, drugs, biological and immunological agents, gene therapy.

Readings/Bibliography

Note: english-speaking students can use original versions of the books, when available.

Recommended

Robbins e Cotran - Le basi patologiche delle malattie. Edra Masson

Alternative

Pontieri, Patologia generale, Piccin

Teaching methods

Lectures.

Assessment methods

Final examination aims to assess the achievement of learning objectives, and therefore the knowledge of the main subjects in:

• Immunology
• Genetic pathology
• Basic oncology, with special emphasis  on molecular oncology

The final grade takes into account the synthesis of final evaluations of different subjects belonging to the integrated course of Immunology and Molecular Pathology. Each single evaluation (performed as oral or written test as to Immunology) is integrated in order to obtain the unique final grade (maximum 30 points). Such grade is the CFU-weighted average of grades obtained in specific questions on main objectives of the integrated course (10 CFU), which consists of the following three subjects: Immunology (5 CFU), Genetic Pathology and Oncology (5 CFU). Examination is passed if the grade in each subjects is not lower than 18 points.

Teaching tools

All the slides shown are available for download.

Office hours

See the website of Patrizia Nanni