cancer genetics

cancer is genetic but

cancer is rarely heritable

What are the checkpoints

cell division checkpoints

Tumor

distinct mass of abnormal cells

that do not have normal controls on cell

division.

Benign

abnormal cells remain localized

and do not invade surrounding tissue.

Malignant

cancer cells invade

surrounding tissue.

metastaic

cancer cells spread and

establish secondary tumors in other sites

in the body.

What are the mainc auses of cancer

gnetic influences and env agents

genetic influences of cancer include

Mutation(s) typically in somatic cells

• Single defective gene

• Polygenic (more than 1 defective gene)

• Chromosome aberration

• Viruses

env agent influences include

altering a gene or altering gene expression

most cancers are

sporadic and influenced by the environment

cancers develop over

time

High correlations between the

number of cell divisions

and

cancer risk among tissues

observed in widely different

environments.

About 2/3 of the Mutations Leading to Cancer are the Result

of

Errors in Replication

Incidence rates around the

world show that migrant

populations take on cancer

rates of

their host country.

Tumor suppressor genes

prevent “bad” cells from dividing.

Proto-oncogenes

allow “good” cells to divide.

loss of function mutations are

Complete or partial absence of protein function

• typically RECESSIVE ACTING

gain of function mutations are

Cell produces protein that is not normally present.

• Either new gene product or gene product in new location or at an

inappropriate time in development.

• DOMINANT ACTING

BRCA1

dna repair transcription factor implicated with breast and ovarian cancer when mutated

p53

regulates cell division apoptosis, DNA repair as associated with many forms of cancer

RB

regulates cell divison and associated with retinoblastoma and cancers

Knudson’s Two Hit

Hypothesis

both copies

have to be defective in same

cell to allow tumor to

develop.

Normal protein responsible

for regulation at G1/S

checkpoint. is the

RB gene

Retinoblastoma implicates 40% of cases

inherited

RB normally prevents E2F

from activating replication.

BRCA1 and BRCA2 are used

to repair double strand breaks.

BRCA1 and BRCA2 account for about

5-10% of all breast cancers.

tumor suppressor p53

functions at the G1 checkpoint

if NDA is damaged p53 delays

cell division until damage is repaired or programs cell to die

Mutation in proto-oncogene results in

in oncogene that allows

uncontrolled cell division

Only a need mutation in 1 copy of a proto-oncogene

to result in a tumor

MYC is a

transcription factor implicated in lymphomas and leukemias

Burkitt’s Lymphoma is a result of

Abnormal function of B cells

in B. lymphoma Reciprocal translocatiom between

chromosomes 8 and 14 places c-

myc (oncogene) next to enhancer. leads to high function of c-myc gene

Retroviruses can:

Mutate and Rearrange proto-oncogenes.

• Insert a strong promoter near proto-oncogenes.

colon cancer

both tumor suppressor and

oncogenes are defective.

Xeroderma pigmentosum is a result of

defective nucelotide excession repair

colorectal, endometrial, and stomach cancers are a result of

defective mismatch repair

BRCA1 AND BRCA2 are a result of

deffectie double strand break repair

Tumor cells often have telomerase expression

, which is thought to

contribute to the “immortality” of cancer cells.

Angiogenesis

(growth of new blood vessels) is important to tumor

progression.

Growth factors and other proteins involved in

angiogenesis are

often overexpressed in tumor cells.

Is it possible to fight cancer by preventing angiogenesis?

Metastasis is the cause of death in 90% of human cancer cases!

CAR-T Cell Therapies

possible cancer treatment

concordant

twins same for the given trait

discordant

twins differ for trait

MYC

a transcription factor

MYC is an

oncogene for lymphomas and leukemias

What are the three tumor supressor genes we know about

BRCA, P53, AND rb

Retroviruses can cause

cancer by mutating and rearranging protooncogenes