Onco 1 - Genetics Of Cancer Flashcards
What cancer is the most common in men?
Prostate. Lung. Colon. (All in that order)
Whats is the most common cancer in women?
Breast. Lung. Colon. Uterus. (All in that order).
What is the most mortal cancer in men?
Lung. Prostate. Colon. Pancreas. (All in that order).
What is the most mortal cancer in women?
Lung. Breast. Colon. Pancreas. (All in that order).
How does cancer occur?
Cancer occurs when a cell undergoes a change so that it keeps dividing.
What happens in the S phase in cell cylcle?
Replication of DNA.
What are two tumor suppressors found in the checkpoint b/w G1 and S phase?
Rb and p53.
How does the cell progress from G1 to S phase?
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.
What happens in the cell cycle where there is a mutation or deletion of the Rb tumor suppressor gene?
It causes uncontrolled cell division.
What is the fundamental cause of malignant transformation?
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.
What are the four main targets of genetic damage that can cause carinogenesis?
Proto-oncogenes. Tumor suppressor genes. Genes that regulate apoptosis. DNA repair genes.
What are Proto-oncogenes?
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.
In the case of tumor suppressor genes, what is required in order to have carcinogenesis?
Requires mutations in both alleles; AKA “Two hits”
What two cancers are associated w/ Rb mutations?
Retinoblastoma. Osteosarcomas.
What is p53 and what does it do?
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.
What happens where there is mutation of p53?
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.
What is associated w/ mutations of the APC tumor suppressor gene?
AKA Adenomatous polyposis coli, it is associated w/ Familial adenomatous polyposis and colon cancer.
What is associated w/ mutations of the BRCA tumor suppressor gene?
Breast Cancer. Ovarian cancer.
What is associated w/ mutations of the DPC tumor suppressor gene?
AKA Deleted pancreatic cancer, it is deleted in pancreatic cancers.
What is associated w/ mutations of the DCC tumor suppressor gene?
AKA Deleted Colon Cancer, its’ deletion is associated w/ colon cancer.
What is associated w/ mutations/deletion of the NF1 tumor suppressor gene?
It’s deletion or mutation causes Neurofibromatosis I. The gene is located in chromosome 17.
What is associated w/ mutations/deletion of the NF2 tumor suppressor gene?
Neurofibromatosis II. Bilateral acoustic Schwannoma. It is on chromosome 22.
What is associated w/ mutations/deletion of the WT1 and WT2 tumor suppressor genes?
Wilms tumor.
What is associated w/ mutations/deletion of the VHL tumor suppressor gene?
Von Hippel-Lindau.
What is associated w/ mutations/deletion of the TSC tumor suppressor gene?
Tuberous sclerosis.
In the case of oncogenes, what is required for carcinogenesis?
Require only one mutation of the allele. So the cells “gain” a function to become cancerous.
What is the most common oncogene abnormality in human tumors?
RAS oncogene. 15-20% of all human tumors contain mutated versions of RAS proteins.
What the does the oncogene mutation K-RAS is associated with?
Colon, lung, and pancreatic tumors (Kolon, panKreatic).
What the does the oncogene mutation H-RAS is associated with?
Bladder and kidney tumors (Hematuria).
What the does the oncogene mutation N-RAS is associated with?
Melanomas and hematologic malignancies.
What does the normal RAS protein do? What happens when it is mutated?
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).
What the does the oncogene mutation K-RAS is associated with?
Colon, lung, and pancreatic tumors (Kolon, panKreatic).
What the does the oncogene mutation H-RAS is associated with?
Bladder and kidney tumors (Hematuria).
What the does the oncogene mutation N-RAS is associated with?
Melanomas and hematologic malignancies.
What does the normal RAS protein do? What happens when it is mutated?
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).
