Molecular Basis of Carcinogenesis I Flashcards
Atypia
abnormal morphological or microscopic characteristics of a cell or tissue. May or may not be a precursor for cancer
Metaplasia
an adaptive substitution of one type of adult cell with another, typically in response to stress or inflammation. Not a precursor for cancer!
Dysplasia
an abnormal cellular proliferation altering cellular architecture and sub cellular characteristics. Often but not always a pre-neoplastic cancer precursor
Histogenesis
origin and development of tissues, tumors or cancer. Includes: tissue/organ system; phenotypic/biologic cellular differentiation; microscopic features or biomarker based subtypes
Anaplasia
loss of structural/functional differentiation, typically seen in malignant neoplasms
Tumor
non-specific term meaning lump or swelling. Not a synonym of cancer
Neoplasm
new growth or an aberrant proliferation of cells. Not a synonym for cancer
Neoplasia
process of clonal expansion leading to new growth, often used as a non-specific term similar to the word tumorigenesis. Not a synonym for carcinogenesis
Cancer
a malignant cellular process exhibiting properties that may lead to host destruction or death through uncontrolled growth and destruction of normal tissue or function
What are the clinical properties of cancer?
- uncontrolled growth resulting in a mass
- alterations in mechanisms of cell death and senescence
- invasion
- metastases
- tendency to recur after excision
- clonal expansion over time and in response to treatment
- change in cellular phenotype with time and treatment
- ability to cause significant illness or death
- angiogenesis (induce growth of new vessels)
What is carcinogenesis?
- associated with the accumulation of many somatic genetic alterations (multi-hit genetic error as a requisite for the development of cancer)
- multistep - initiation and progression
Describe the initiation step in carcinogenesis
- occurs as a result of mutation or loss of function of critical genes in a single cell
- followed by cellular proliferation
- involved in errors in oncogenes or tumor suppressor genes
Describe the progression step in carcinogenesis
- clonal cancer cells incur additional genetic errors and selection factors create multiple clones within the cancerous cell population
What type of cells are most likely to transform into cancer?
ectodermal derived cells (epithelial cells). Known as carcinoma
Loss of heterozygosity
- frequent mechanism by which cancer susceptibility can be inherited
- can be defined as the physical loss (or functional inactivation) of one of two copies of a gene
- a mechanism of genetic damage associated with many subtypes of heritable human cancer
Where is the retinoblastoma gene located?
chromosome 13
What does mutation in the RB gene cause?
- retinoblastoma, ocular (eye) cancer
- No RB protein, so cells cannot down regulate their cell division and so they grow out of control
What happens when the RB protein is hyper-phosphorylated?
the cell can proliferate and enter S to G2 phases of the cell cycle
What happens with the RB protein is hypo-phosphorylated?
the cell is stuck in G0 and G1 phase and RB represses the entry of cells into the S phase of the cell cycle
What is the hallmark pattern of cancer arising from loss of a tumor suppressor gene?
- normal, non-malignant retinal cells are heterozygous for the retinoblastoma gene
- cancer cells are homozygous for loss of RB gene
What happens to people who are heterozygous for the RB gene?
- they are likely to develop the disease (gain another mutation)
- there is a 50% chance they will pass the defect on to their children
What happens to people who have a sporadic case of retinoblastoma?
usually they will have unilateral retinoblastoma
