Neoplasia III Flashcards
BCL2. What is it and how is it activated?
The prototypic anti-apoptosis gene
Can be activated by translocation from chromosome 18 to the Ig heavy chain locus on chromosome 14
What happens when BCL2 is over-expressed?
Protects cells from apoptosis, allowing them to survive for prolonged periods
Results in steady accumulation of cells - often seen in “low-grade” lymphomas
Tumors grow slowly not because cells are proliferating, they just aren’t dying
Sustained Angiogenesis
Even with multiple genetic abnormalities, tumors cannot exceed 1-2 mm in diameter unless they are vascularized
Angiogenesis facilitates metastases - provides access to the vasculature
T/F - all cells are capable of metastasizing
False - Only certain subclones may be capable of metastasizing
What are the two phases of Invasion and Metastasis?
1) Invasion of ECM
2) Vascular dissemination and adhesion/homing of tumor cells
Steps of Invasion of ECM
1) Tumor cells detach from one another
2) They attach to ECM components (collagens, glycoproteins, and proteoglycans)
3) They degrade matrix components
4) Migration of tumor cells
Once in circulation, tumor cells are vulnerable to what?
Destruction by the host immune cells
How can the distribution of tumor metastases be predicted?
Based of the location of the primary tumor and its vascular and/or lymphatic drainage
Organ tropism
Sometimes seen in metastases
a. Organ-specific endothelial adhesion molecules bind tumor cell ligands
b. Chemokine receptors on tumor cells home to tumor cells home to sites where specific ligands are readily produces
What is critical to integrity of genome and control of cellular growth?
DNA repair
Patients with inherited defects in DNA repair have what?
Increased risk for cancer
If errors in DNA replication occur naturally, why isn’t cancer more common?
DNA repair genes - they’re pretty reliable
Hereditary nonpolyposis colon cancer sydrome
Familial cancers of the colon resulting from defective genes involved in DNA mismatch repair and evidence of microsatellite instability
Xeroderma pigmentosum
Defective nucleotide excision repair system
Sunlight (UV light) causes pyrimidine cross-linking in DNA, halting replication
Lacking ability to excise and repair their altered residues leads XP patients at risk for cancer
Bloom Syndrome, Ataxia telangiectasia, Fanconi anemia
Disorders characterized by hypersensitivity to DNA damage
Patients have increased cancer risk and other health problems
BRCA1 and BRCA2
Genes involved with repair of dsDNA breaks, may also have tumor suppressor roles
Patients are at risk for other forms of cancer besides breast cancer
Multistep carcinogenesis
No single mutation results in cancer
Cancers typically exhibit multiple genetic alterations including activation of several oncogenes and two or more cancer suppressor genes
What is the epidemiological evidence for multiple step carcinogenesis?
Cancer is more likely to occur in older people
Tumor Progression and Heterogeneity
Tumors begin as a monoclonal proliferation of one transformed cell. As daughter cells divide, they tend to develop more and more mutations
By the time a tumor mass is formed, the cells may be quite heterogeneous in many lesions
The subclones may be able to survive certain therapies, invade certain host tissue, or metastasize with greater efficiency
What are the different Karyotypic Changes in Tumors?
Balanced Translocations
Deletions
Gene amplifications
Balanced translocations
Extremely common, especially in hematopoeitic neoplasms
example: CML (philladelphia chromosomes) - translocation between chromosomes 9 and 22, causing 22 to become shorter
Deletions
Second most prevalent form of karyotypic abnormalitites in tumores
example: 3p, 9p, and 17p are common areas of loss in oral cancers
Gene amplifications
Seen in neuroblastoma and some breast cancers
What are the three major classes of carcinogenic agents?
Chemicals
Radiant energy
Oncogenic viruses
