01132 - Molecular Pathology - Immunology (Integrated Course) (LZ-A)

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) and an Oncology part (3 credits, Prof. Lollini and Nanni). The following program refers to 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: promoter methylation, long non-coding RNAs, RNA interference. Genomic imprinting: the Prader-Willi and Angelman syndromes. Protein glycosylation and outline on congenital diseases of glycosylation (CDGs). 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

Robbins & Cotran Pathologic Basis of Disease 9th edition

Teaching methods

A total of 40 hours of lectures in groups of 2 hours of which 16 of Genetic Pathology (Dall'Olio) and 24 of Oncology (Lollini and Nanni). Slides available on Insegnamenti OnLine.

Assessment methods

Oral examination at the end of the course. The rank of Molecular Pathology will be the mean of the ranks obtained in Genetic Pathology and Oncology. This rank will be mediated with the rank of Immunology. The dates of the exams are published on AlmaEsami.

Teaching tools

The most appropriate textbook for this course is the Robbins-Cotran, The pathological basis of disease, 9th edition, Elsevier. However, since many topics of the course are not appropriately covered by the textbook, it is essential the attendance to the course.

Office hours

See the website of Fabio Dall'Olio