Onco 1 - Genetics Of Cancer

Question 1

What cancer is the most common in men?

Answer 1

Prostate. Lung. Colon. (All in that order)

Question 2

Whats is the most common cancer in women?

Answer 2

Breast. Lung. Colon. Uterus. (All in that order).

Question 3

What is the most mortal cancer in men?

Answer 3

Lung. Prostate. Colon. Pancreas. (All in that order).

Question 4

What is the most mortal cancer in women?

Answer 4

Lung. Breast. Colon. Pancreas. (All in that order).

Question 5

How does cancer occur?

Answer 5

Cancer occurs when a cell undergoes a change so that it keeps dividing.

Question 6

What happens in the S phase in cell cylcle?

Answer 6

Replication of DNA.

Question 7

What are two tumor suppressors found in the checkpoint b/w G1 and S phase?

Answer 7

Rb and p53.

Question 8

How does the cell progress from G1 to S phase?

Answer 8

Cyclin D activates CDK4. Active kinase complex phosphorylates Rb protein. Phosphorylated Rb protein comes unbound from E2F, which allows cell to progress to S phase.

Question 9

What happens in the cell cycle where there is a mutation or deletion of the Rb tumor suppressor gene?

Answer 9

It causes uncontrolled cell division.

Question 10

What is the fundamental cause of malignant transformation?

Answer 10

AKA Carcinogenesis, it is fundamentally due to nonlethal genetic damage. The malignant tumors are derived from clonal expansion of a single precursor cell. Malignant transformation is a multistep process, resulting from multiple mutations. The individual cells in a single tumor have varying degrees of malignant potential.

Question 11

What are the four main targets of genetic damage that can cause carinogenesis?

Answer 11

Proto-oncogenes. Tumor suppressor genes. Genes that regulate apoptosis. DNA repair genes.

Question 12

What are Proto-oncogenes?

Answer 12

Normal genes that that regulate cell proliferation and differentiation, and when mutated, become oncogenes, which allows the cell to be autonomous (no need for outside stimuli or normal mitotic signals) to grow and divide. Oncoproteins produced from these genes are devoid of important regulator elements.

Question 13

In the case of tumor suppressor genes, what is required in order to have carcinogenesis?

Answer 13

Requires mutations in both alleles; AKA “Two hits”

Question 14

What two cancers are associated w/ Rb mutations?

Answer 14

Retinoblastoma. Osteosarcomas.

Question 15

What is p53 and what does it do?

Answer 15

It is a tumor suppressor gene that acts thru p21 to cause cell-cycle arrest in the G1/S phase checkpoint and G2/M checkpoint. It causes apoptosis by inducing the transcription of pro-apoptotic genes (such as BAX). They call this gene the guardian of the genome.

Question 16

What happens where there is mutation of p53?

Answer 16

Mutations in this gene allow the cell to progress thru the check points despite the presence of DNA damage/mutations. Mutations of this gene are seen in more than 50% of human cancers.

Question 17

What is associated w/ mutations of the APC tumor suppressor gene?

Answer 17

AKA Adenomatous polyposis coli, it is associated w/ Familial adenomatous polyposis and colon cancer.

Question 18

What is associated w/ mutations of the BRCA tumor suppressor gene?

Answer 18

Breast Cancer. Ovarian cancer.

Question 19

What is associated w/ mutations of the DPC tumor suppressor gene?

Answer 19

AKA Deleted pancreatic cancer, it is deleted in pancreatic cancers.

Question 20

What is associated w/ mutations of the DCC tumor suppressor gene?

Answer 20

AKA Deleted Colon Cancer, its’ deletion is associated w/ colon cancer.

Question 21

What is associated w/ mutations/deletion of the NF1 tumor suppressor gene?

Answer 21

It’s deletion or mutation causes Neurofibromatosis I. The gene is located in chromosome 17.

Question 22

What is associated w/ mutations/deletion of the NF2 tumor suppressor gene?

Answer 22

Neurofibromatosis II. Bilateral acoustic Schwannoma. It is on chromosome 22.

Question 23

What is associated w/ mutations/deletion of the WT1 and WT2 tumor suppressor genes?

Answer 23

Wilms tumor.

Question 24

What is associated w/ mutations/deletion of the VHL tumor suppressor gene?

Answer 24

Von Hippel-Lindau.

Question 25

What is associated w/ mutations/deletion of the TSC tumor suppressor gene?

Answer 25

Tuberous sclerosis.

Question 26

In the case of oncogenes, what is required for carcinogenesis?

Answer 26

Require only one mutation of the allele. So the cells “gain” a function to become cancerous.

Question 27

What is the most common oncogene abnormality in human tumors?

Answer 27

RAS oncogene. 15-20% of all human tumors contain mutated versions of RAS proteins.

Question 28

What the does the oncogene mutation K-RAS is associated with?

Answer 28

Colon, lung, and pancreatic tumors (Kolon, panKreatic).

Question 29

What the does the oncogene mutation H-RAS is associated with?

Answer 29

Bladder and kidney tumors (Hematuria).

Question 30

What the does the oncogene mutation N-RAS is associated with?

Answer 30

Melanomas and hematologic malignancies.

Question 31

What does the normal RAS protein do? What happens when it is mutated?

Answer 31

Is part of a G-protein in a growth factor receptor. Growth factor binds the receptor and the RAS G-protein activates MAP kinase (mitogen-activated protein kinase), causing stimulation of cell proliferation. This has to be a temporary activated; the GTP should be hydrolyzed to GDP (this is turned on eternally when mutated, so the cells keep proliferating).

Question 32

What the does the oncogene mutation K-RAS is associated with?

Answer 32

Colon, lung, and pancreatic tumors (Kolon, panKreatic).

Question 33

What the does the oncogene mutation H-RAS is associated with?

Answer 33

Bladder and kidney tumors (Hematuria).

Question 34

What the does the oncogene mutation N-RAS is associated with?

Answer 34

Melanomas and hematologic malignancies.

Question 35

What does the normal RAS protein do? What happens when it is mutated?

Answer 35

Is part of a G-protein in a growth factor receptor. Growth factor binds the receptor and the RAS G-protein activates MAP kinase (mitogen-activated protein kinase), causing stimulation of cell proliferation. This has to be a temporary activated; the GTP should be hydrolyzed to GDP (this is turned on eternally when mutated, so the cells keep proliferating).