Molecular Basis of Carcinogenesis I

Question 1

Atypia

Answer 1

abnormal morphological or microscopic characteristics of a cell or tissue. May or may not be a precursor for cancer

Question 2

Metaplasia

Answer 2

an adaptive substitution of one type of adult cell with another, typically in response to stress or inflammation. Not a precursor for cancer!

Question 3

Dysplasia

Answer 3

an abnormal cellular proliferation altering cellular architecture and sub cellular characteristics. Often but not always a pre-neoplastic cancer precursor

Question 4

Histogenesis

Answer 4

origin and development of tissues, tumors or cancer. Includes: tissue/organ system; phenotypic/biologic cellular differentiation; microscopic features or biomarker based subtypes

Question 5

Anaplasia

Answer 5

loss of structural/functional differentiation, typically seen in malignant neoplasms

Question 6

Tumor

Answer 6

non-specific term meaning lump or swelling. Not a synonym of cancer

Question 7

Neoplasm

Answer 7

new growth or an aberrant proliferation of cells. Not a synonym for cancer

Question 8

Neoplasia

Answer 8

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

Question 9

Cancer

Answer 9

a malignant cellular process exhibiting properties that may lead to host destruction or death through uncontrolled growth and destruction of normal tissue or function

Question 10

What are the clinical properties of cancer?

Answer 10

• 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)

Question 11

What is carcinogenesis?

Answer 11

• 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

Question 12

Describe the initiation step in carcinogenesis

Answer 12

• 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

Question 13

Describe the progression step in carcinogenesis

Answer 13

• clonal cancer cells incur additional genetic errors and selection factors create multiple clones within the cancerous cell population

Question 14

What type of cells are most likely to transform into cancer?

Answer 14

ectodermal derived cells (epithelial cells). Known as carcinoma

Question 15

Loss of heterozygosity

Answer 15

• 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

Question 16

Where is the retinoblastoma gene located?

Answer 16

chromosome 13

Question 17

What does mutation in the RB gene cause?

Answer 17

• retinoblastoma, ocular (eye) cancer

- No RB protein, so cells cannot down regulate their cell division and so they grow out of control

Question 18

What happens when the RB protein is hyper-phosphorylated?

Answer 18

the cell can proliferate and enter S to G2 phases of the cell cycle

Question 19

What happens with the RB protein is hypo-phosphorylated?

Answer 19

the cell is stuck in G0 and G1 phase and RB represses the entry of cells into the S phase of the cell cycle

Question 20

What is the hallmark pattern of cancer arising from loss of a tumor suppressor gene?

Answer 20

• normal, non-malignant retinal cells are heterozygous for the retinoblastoma gene
• cancer cells are homozygous for loss of RB gene

Question 21

What happens to people who are heterozygous for the RB gene?

Answer 21

• they are likely to develop the disease (gain another mutation)
• there is a 50% chance they will pass the defect on to their children

Question 22

What happens to people who have a sporadic case of retinoblastoma?

Answer 22

usually they will have unilateral retinoblastoma