Intro to Neoplasia and Molecular Basis of Cancer Flashcards
Neoplasm
Clonal proliferation of cells exhibiting uncontrolled growth
Malignant neoplasm
Cancer
Carcinogens
Cause DNA damage leading to uncontrolled cell growth by acting on specific pathways that control cell growth
Benign tumor
- circumscribed
- uncontrolled growth but does not invade adjacent tissue
- well differentiated and resemble tissue of origin
- slow growth rate
Malignant tumor
- poorly defined
- infiltrates adjacent tissue
- poorly or well differentiated
- fast growth rate
What factors determine tumor growth rate?
- Proportion of dividing cells
- Rate of division
- Ratio of division to death
Dysplasia
- Disordered growth usually associated with the epithelium
- May progress to malignant neoplasm
Metastasis
- Defining quality of malignant neoplasms
- Spreading requires a repertoire of abilities acquired through accumulation of mutations
Routes of metastatic spread
- Lymphatic
- Hematogenous
- Seeding of body cavities
Oncogene
- Mutated gene that promotes autonomous cell growth in cancer cells
Proto-oncogene
Normal counterpart of an oncogene; essential for cell growth and differentiation and still under normal regulatory control
How can a proto-oncogene become an oncogene
- Translocation or transposition to a new promoter => normal growth stimulating protein in excess
- Gene amplification => normal growth stimulating protein in excess
- Point mutation within a control element => normal growth stimulating protein in excess
- Point mutation within the gene => hyperactive or degradation-resistant protein
Oncoprotein
Promotes cell growth in the absence of normal growth promoting signals
Tumor suppressor genes
Encode proteins that prevent uncontrolled cell growth and division at checkpoints (p53, RB)
What kind of mutations are found in oncogenes?
- Activating mutations are usually missense
- Overexpression caused by translocation or amplification
- Activation by translocation and formation of a fusion protein
What kind of mutations are found in tumor suppressor genes?
- Loss of function variants
- Deletions
Two hit hypothesis
For cancer, both copies of a gene must be damaged
Two hit hypothesis: sporadic cancer
Each copy of a gene is damaged individually (sequentially)
Two hit hypothesis: hereditary cancer
One damaged gene is inherited and the second copy is damaged individually
Tumor testing
- identifies somatic changes
- sample = tumor tissue
- provides diagnostic/prognostic information
Germline testing
- identifies germline mutations
- sample = blood or skin cells
- gives info about familial cancer risk
Cancer predisposition syndromes associated with mutations in oncogenes
Autosomal dominant:
- Multiple endocrine neoplasia type II
- hereditary neuroblastoma
- costello syndrome
- cardio-facio-cutaneous syndrome
- hereditary papillary renal cell cancer
Cancer predisposition syndromes associated with mutations in tumor suppressors
Autosomal dominant:
- retinoblastoma
- li fraumeni syndrome
- hereditary breast/ovarian cancer
- familial adenomatous polyposis
- cowden syndrome - PTEN hamartoma syndrome
pRB
- Tumor suppressor gene
- Inhibits G1 -> S transition via a cyclin D-Cdk4/6 mediated mechanism
p53
- tumor suppressor gene
- activated by stress: DNA damage, oncogene activation, hypoxia
- induces apoptosis
Cancer predisposition syndromes associated with chromosome instability
All are autosomal recessive:
- Ataxia telangiectasia
- Fanconi anemia
- Nijmegen breakage syndrome
- Bloom’s syndrome
