Ch. 15 Cancer Genetics and Genomics

Flashcards about cancer genetics and genomics.

Define

1. Neoplasia

2. Malignant

1. Disease process characterized by uncontrolled cellular proliferation leading to a mass/tumor.

2. Neoplasm that exhibits uncontrolled growth, is capable of invading neighboring tissues, and can metastasize to more distant sites.

Describe the listed classes of cancer:

1. Carcinoma

2. Sarcoma

3. Hematopoietic and lymphoid

1. Originate in epithelial tissue, such as lining intestine, bronchi, or mammary ducts.

2. Bone, muscle, connective tissue, nervous system.

3. Bone marrow, lymphatic system, and peripheral blood.

Environmental agents can act as mutgens.

1. Where was this data pulled from?

2. Name some environmental agents

1. data from Hiroshima and Nagasaki - as much as 75% of the risk of cancer is related to environmental in origin

2. Radiation, Chemical carcinogens - cigs/vapes, pesticides/chemical solvents/industrial fertilizers, burnt meat and deli meat

Passenger Mutations vs Driver Mutations

Passenger: Random, not recurrent mutations that probably occur as the cancer develops. (picked up on the way)

Driver: Mutations involved in the development or progression of cancer

• caused by any type of mutation

• environmental agents increase rate of mutation

What are processes affected by driver mutations?

• any point in the cycle can be affected

  • cell cycle regulation

  • cell proliferation

  • differentiation

  • exit from cell cycle

  • growth inhibition by cell-cell contacts

  • apoptosis

1. What are Proto-oncogenes

2. What are tumor suppressor genes

3. What is the two hit hypothesis?

Form of Driver genes

• Proto-oncogenes - Normal genes that lead to excessive cell proliferation if mutated

  • stimulate proliferation or inhibit apoptosis

• Tumor suppressor genes - stimulate apoptosis when DNA is damaged (under normal conditions)

  • typically require mutations in both alleles

• Two hit theory is of TSG inactivation (insinuates, TSG contributes to cancer development)

  • one hit is typically the inheritance of 1 mutated allele (germline mutation)

  • second hit is most commonly somatic mutation of the other allele

Two hit theory is categorized as _______

Loss of heterozygosity

T/F: Genetic “rules” stop being followed within cancer cells because the cell becomes destabilized leading to more mutation

true

T/F: Different cells within a tumor can only have one specific mutation

false - can have different mutations (due to genetic instability)

Describe how mutations in RET contribute to the development of Multiple Endocrine Adenomatosis

• RET encodes a cell-surface protein that can bind signaling molecules to activate a cell signaling pathway. BUT a mutation in the RET can cause the pathway to always be on

  • suppresses apoptosis and stimulates proliferation

• MEA occurs from mutations in the RET gene

What is Retinoblastoma?

How does mutations in RB1 contribute to it?

1. Rare malignant tumor in the retina of a child.

2. RB1 gene regulates entry into S phase of the cell cycle but the mutation losses the checkpoint and allows uncontrolled proliferation

   1. 40% are heritable with mutation on chromo 13

   2. 60% are sporadic with both RB1 alleles must be mutated int he same somatic cell

What percentage of retinoblastoma cases are of the heritable form?

What percent are sporadic?

1. 40%

2. 60%

Describe the functions of BRCA1 and BRCA 2 under normal conditions in a cell

BRCA 1 and BRCA 2 are tumor suppressor genes under normal conditions - repair double stranded DNA breaks

Describe BRCA1

Accounts for 1/2 of autosomal dominant familial breast cancer.

Describe BRCA2

Accounts for 1/3 of autosomal dominant familial breast cancer.

1. What is Familial Adenomatous Polyposis (FAP)?

2. How do mutations occur?

1. Autosomal dominant colon cancer.

   1. Benign polyps form by age 20 and become malignant over time

2. Caused by a loss-of-function mutation in the APC gene.

Describe Xeroderma Pigmentosum (XP)

• mutation in the tumor suppressor gene causing an autosomal recessive disease

• Impaired nucleotide excision repair - the “bump” is cut out but the repair becomes a mutation

• UV induced damage to the skin

How doe mutations in the RAS Gene contribute to cancer?

causing permanent activation of cell growth signals, leading to uncontrolled cell division

• mutated RAS gene are found in 30% of cancers

1. How can cancer be initaiated by translocation?

2. What is the Philadelphia Chromosome?

1. Chromosome is translocatedand leads to the formation of the BCR-ABL fusion gene that promotes uncontrolled cell proliferation.

2. Translocation between chromosomes 9 and 22, associated with chronic myelogenous leukemia.

How is telomerase implicated in cancer?

What is the significance of TP53?

1. Telomerase persistence found in tumors allows them to proliferate indefinitely creating “immortal” cells, bypassing normal cellular aging.

2. TP53, known as the "guardian of the genome," is a tumor suppressor gene that regulates the cell cycle and prevents genomic mutations. Mutations in TP53 can lead to the loss of this regulatory function, contributing to cancer progression.

______ gene is frequently mutated in sporadic and familial cancers

RB1

Describe the significance of gene expression profiling of tumors in cancer therapy.

• it will discriminate between different tumors

• correlate with known clinical outcomes and help guide therapy

• may reveal unsuspected connections of functional importance

What is meant by targeted or precision cancer therapy?

Determine which cellular pathway the tumor is using to replicate and target the specific pathway