Major classes of cancer genes

Question 1

What are the three major categories of cancer-causing genes?

Answer 1

Tumor suppressors, oncogenes, DNA repair genes

Question 2

What is the function of tumor suppressor genes?

Answer 2

Control cell division and help prevent tumors

Question 3

How are inherited mutations of tumor suppressor genes characterized at the individual level?

Answer 3

Dominant alleles

Question 4

How are inherited mutations of tumor suppressor genes characterized at the cellular level?

Answer 4

Recessive alleles

Question 5

What is required for tumor formation in individuals with an inherited RB1 mutation?

Answer 5

A second hit in any one cell

Question 6

What is the average effect of heterozygous inheritance of the RB1 mutation?

Answer 6

Formation of several retinoblasts homozygous for an RB1 mutation

Question 7

What is the penetrance of the retinoblastoma mutation?

Answer 7

90%

Question 8

What is the role of the RB1 protein (pRb) in the cell cycle?

Answer 8

Acts as a master brake by binding to E2F transcription complex

Question 9

What is the effect of phosphorylation on pRb?

Answer 9

Inactivation of pRb

Question 10

What is a general property of tumor suppressors?

Answer 10

Block uncontrolled cellular proliferation that can lead to cancer

Question 11

What happens when both alleles of a tumor suppressor gene are inactivated?

Answer 11

Uncontrolled cellular proliferation

Question 12

How do oncogenes differ from tumor suppressor genes in terms of mutation effects?

Answer 12

Oncogenes have gain-of-function mutations, while tumor suppressors have loss-of-function mutations

Question 13

What is required for oncogenes to contribute to tumor progression?

Answer 13

Only one copy of a mutated oncogene

Question 14

What are the four basic regulators of normal cell growth related to proto-oncogenes?

Answer 14

• Growth factors
• Growth factor receptors
• Signal transduction molecules
• Nuclear transcription factors

Question 15

How are oncogenes typically activated?

Answer 15

Gain-of-function mutations, gene amplification, hypomethylation, chromosome rearrangements

Question 16

What common observation in tumor cells leads to identifying oncogenes?

Answer 16

Chromosomal rearrangements such as translocations

Question 17

What is the role of the RAS protein in cell growth?

Answer 17

Cycles between active (GTP-bound) and inactive (GDP-bound) forms

Question 18

What is the consequence of RAS mutations?

Answer 18

RAS protein remains in the active form, leading to excessive cell division

Question 19

What is the Philadelphia chromosome associated with?

Answer 19

Translocation between chromosomes 9 and 22 leading to chronic myelogenous leukemia

Question 20

What disease is associated with mutations in the TP53 tumor suppressor gene?

Answer 20

Li–Fraumeni syndrome

Question 21

Fill in the blank: Tumor suppressor genes are usually _______ at the cellular level.

Answer 21

Recessive

Question 22

Fill in the blank: Oncogenes are usually _______ at the cellular level.

Answer 22

Dominant

Question 23

What is the function of BRCA1 and BRCA2 genes?

Answer 23

Involved in DNA repair

Question 24

What is the role of the mutant RAS protein in cell division?

Answer 24

The mutant RAS protein cannot extinguish its growth signal, contributing to excessive cell division.

Question 25

What is a common observation in tumor cells that helps identify oncogenes?

Answer 25

Chromosomal rearrangements, such as translocations.

Question 26

What is the Philadelphia chromosome?

Answer 26

A translocation between chromosomes 9 and 22 that places the ABL proto-oncogene next to the BCR gene, enhancing tyrosine kinase activity and producing chronic myelogenous leukemia.

Question 27

How do retroviruses contribute to cancer?

Answer 27

They can insert oncogenes into the DNA of a host cell, transforming the host into a tumor-producing cell.

Question 28

What is genomic instability?

Answer 28

A condition characterized by widespread mutations, chromosome breaks, and aneuploidy in tumor cells.

Question 29

What are some genetic factors that can lead to genomic instability?

Answer 29

* Defects in proteins required for accurate cell division * Defects in proteins responsible for DNA repair * Hypomethylation of DNA

Question 30

Which genes are commonly associated with defective repair of double-stranded breaks in DNA?

Answer 30

* BRCA1 * BRCA2 * ATM

Question 31

What is the role of telomeres in cell division?

Answer 31

Telomeres shorten with each cell division, limiting the number of divisions a cell can undergo.

Question 32

What can result from defects in proteins responsible for chromosome separation during mitosis?

Answer 32

Multiple aneuploidies typically seen in tumor cells.

Question 33

What is a characteristic feature of tumors related to genomic instability?

Answer 33

Aneuploidy can create extra copies of oncogenes or delete tumor suppressor genes.

Question 34

What is the typical limit on the number of mitotic divisions for a cell?

Answer 34

About 50 to 70 mitotic divisions.