Genetics Basics and Cell Cycle Overview

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Questions and Answers

What is the definition of an allele?

A specific location on a chromosome.

A version of a gene. (correct)

A nucleotide sequence that encodes proteins.

A tightly packed form of DNA.

What structure has tightly packed DNA?

Chromatid

Nucleotide

Chromosome (correct)

Gene

What is the primary building block of DNA?

Chromatid

Nucleotide (correct)

Chromosome

Gene

What contains the instructions to make a particular protein?

Gene Signup and view all the answers

How many chromosomes do most human cells typically contain?

46 Signup and view all the answers

How many chromatids does a human chromosome usually have?

2 Signup and view all the answers

Which molecules are primarily responsible for regulating the cell cycle?

Cyclins and cyclin-dependent kinases Signup and view all the answers

What describes the role of protein kinases in signaling pathways?

They catalyze protein phosphorylation. Signup and view all the answers

What are the basic functional units of heredity called?

Genes Signup and view all the answers

How many chromosomes are typically found in the nucleus of human cells?

46 Signup and view all the answers

Which of the following processes occurs to prepare for cell division?

DNA replication Signup and view all the answers

What percentage of genes do most people share?

99% Signup and view all the answers

What term describes variations of a single gene?

Alleles Signup and view all the answers

Which of the following is NOT considered a target of gene mutation in carcinogenesis?

Hormones Signup and view all the answers

What is the structural role of chromosomes in a cell?

Store genetic information Signup and view all the answers

What determines the specific functions of proteins built from genes?

The sequence of nucleotide bases Signup and view all the answers

Which characteristic is associated with Lynch syndrome colorectal carcinoma?

It exhibits microsatellite instability-high (MSI-H). Signup and view all the answers

What role do BRCA1 and BRCA2 proteins play in cellular function?

They are involved in DNA repair via homologous recombination. Signup and view all the answers

Which of the following describes microsatellite instability?

It specifically affects repetitive DNA sequences. Signup and view all the answers

What is the primary mechanism through which cancer-causing mutations accumulate?

Via complementary driver mutations over time. Signup and view all the answers

Which of the following best describes the types of genes that are often targets in cancer-causing mutations?

Regulatory genes performing various functions. Signup and view all the answers

Which type of mutation primarily transforms proto-oncogenes into oncogenes?

Gain-of-function mutations Signup and view all the answers

Which mutation is most commonly associated with the BRAF gene?

BRAFV600E mutation Signup and view all the answers

What specific amino acid change occurs due to the BRAFV600E mutation?

Valine to glutamate Signup and view all the answers

What role does MYC play in cellular biology?

Activates genes involved in cell growth Signup and view all the answers

Which of the following is NOT typically considered an oncogenic substance?

Tumor suppressor genes Signup and view all the answers

Which signaling pathway alteration is present in a significant percentage of ameloblastomas?

MAPK pathway Signup and view all the answers

What is the primary function of telomerase in cancer cells?

Increases telomere length Signup and view all the answers

What does the term 'oncogene' signify in cancer biology?

A gene that promotes autonomous cell growth Signup and view all the answers

What is the primary role of tumor suppressor genes?

To apply brakes to cell proliferation Signup and view all the answers

According to the Knudson ‘two-hit’ hypothesis, how many alleles of a tumor suppressor gene must be mutated to initiate tumor development?

Two Signup and view all the answers

Which type of mutation is characterized by being able to be passed on to subsequent generations?

Germline mutation Signup and view all the answers

What is the significance of the p53 protein in cellular functions?

It induces growth arrest and DNA repair Signup and view all the answers

Which tumor suppressor gene is associated with familial retinoblastoma syndrome?

RB Signup and view all the answers

What condition is characterized by a mutation in the APC gene and numerous adenomatous colonic polyps?

Familial adenomatous polyposis (FAP) Signup and view all the answers

Which of the following cancers is most commonly associated with mutations in the TP53 gene?

Human cancers in general Signup and view all the answers

What is the mechanism of inactivation for the NF2 tumor suppressor gene in meningioma?

Gene deletion Signup and view all the answers

What effect does CDK4 overexpression have on the cell cycle?

It promotes progression through the cell cycle Signup and view all the answers

What type of genetic change is observed in liposarcoma involving MDM2?

Gene amplification Signup and view all the answers

Which syndrome is characterized by multiple epidermoid cysts, osteomas, and supernumerary teeth?

Gardner syndrome Signup and view all the answers

What type of mutation affects a gene within any cell of the body, but cannot be passed on to subsequent generations?

Somatic mutation Signup and view all the answers

Which tumor suppressor gene is directly involved in the regulation of the Wnt/β-catenin signaling pathway?

APC Signup and view all the answers

Study Notes

Genetics Basics

A gene is a distinct DNA sequence within a chromosome that acts as an instruction to make proteins.
Humans have 20,000-25,000 genes (~2 million DNA bases).
Alleles are variations of a single gene with small differences in DNA base sequences.
Humans have 46 chromosomes (23 pairs), half from the mother and half from the father.
A chromosome is a tightly packed structure of DNA.
Each chromosome has two arms and is further divided into regions, bands, and sub-bands, where each gene resides.
A nucleotide is the building block of DNA.

Cell Cycle

The cell cycle is a series of events that take place in a cell as it grows and divides into two daughter cells.
The G0 (resting) phase is where the cell spends most of its time.
The cell cycle is regulated by a complex balance of cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors.

Genetic Basis of Neoplasia

Neoplasia is caused by mutations in normal regulatory genes.
Four classes of genes are commonly targeted in cancer-causing mutations:
- Proto-oncogenes: Growth-promoting genes
- Tumor suppressor genes: Growth-inhibiting genes
- Genes that regulate apoptosis (programmed cell death)
- Genes involved in DNA repair

Proto-oncogenes

Proto-oncogenes are normal genes that promote cell growth.
Oncogenes are mutated proto-oncogenes.
Oncoproteins promote cell growth independently of normal extracellular growth-promoting signals.
The MAPK signaling pathway is altered in a large percentage of ameloblastomas.
BRAF mutations are one of the most common oncogenes.
BRAFV600E is a common mutation found in 90% of all BRAF mutations observed in neoplasia.

Tumor Suppressor Genes

Tumor suppressor genes normally inhibit cell proliferation.
Mutations inactivating tumor suppressor genes lead to a failure of growth inhibition.
The Knudson ‘two-hit’ hypothesis states that both alleles of a tumor suppressor gene must be mutated for tumor development.
Loss-of-function mutations render tumor suppressor proteins unable to function properly.

RB (Retinoblastoma)

RB is a tumor suppressor gene involved in regulating cell cycle progression.
RB is directly or indirectly inactivated in most human cancers.
RB regulates the expression of genes necessary for dividing cells to pass through the G1/S cell cycle checkpoint.

Tumor Suppressor Syndromes

Many cancer predisposition syndromes are characterized by germline mutations in tumor suppressor genes.
Germline mutations are present in every cell of the body and can be passed on to subsequent generations.
Patients with germline mutations in tumor suppressor genes are at increased risk for tumor development.
Examples of tumor suppressor syndromes include:
- Familial adenomatous polyposis (FAP)
- Neurofibromatosis 1 (NF1)
- Nevoid basal cell carcinoma syndrome (Gorlin syndrome)
- Cowden syndrome
- Familial retinoblastoma syndrome
- Li-Fraumeni syndrome

PTCH (Patched 1)

PTCH is a tumor suppressor gene that regulates the Hedgehog signaling pathway.
The PTCH protein binds to and inactivates SMO (a proto-oncogene).
Mutations in PTCH are associated with nevoid basal cell carcinoma syndrome (Gorlin syndrome).

APC (Adenomatous Polyposis Coli)

APC is a tumor suppressor gene that downregulates the Wnt/β-catenin signaling pathway.
FAP is a cancer predisposition syndrome caused by germline mutations in APC.
FAP patients develop multiple adenomatous colonic polyps, with a high risk of transformation to colorectal carcinoma.
APC mutations are also frequently found in sporadic colorectal carcinoma.

Gardner Syndrome

Gardner syndrome is a subgroup of familial adenomatous polyposis syndrome.
It is characterized by multiple epidermoid cysts, osteomas, supernumerary teeth, and multiple premalignant colorectal polyps that have a 100% risk of becoming malignant if untreated.

TP53 (Tumor Protein P53)

TP53 is a tumor suppressor gene known as the 'guardian of genomic stability'.
TP53 regulates cell cycle progression, DNA repair, cellular senescence, and apoptosis.
TP53 monitors DNA damage and cell stress, inducing growth arrest, DNA repair, or apoptosis if DNA cannot be repaired.
TP53 is the most frequently mutated gene in human cancers.

Gene Deletions: Meningioma

Meningioma is the most common brain tumor.
Deletions in 22q, which contains the NF2 tumor suppressor gene, are commonly observed in meningioma.

Gene Amplification: Liposarcoma

Gene amplification is an abnormal generation of multiple copies of a specific DNA sequence.
12q13-15 amplification is seen in liposarcoma.
MDM2 is a negative regulator of TP53.
Amplification of MDM2 can have the same effect as a TP53 mutation.

CDK4 Overexpression

CDK4 overexpression promotes uncontrolled cell cycle progression, contributing to tumor development.

MMR (Mismatch Repair) and Microsatellite Instability

Mismatch repair (MMR) genes are important for repairing DNA mismatches during replication.
Lynch syndrome is a cancer predisposition syndrome associated with mutations in MMR genes.
Lynch syndrome often leads to microsatellite instability (MSI), where repetitive DNA sequences are prone to mutations.
MSI is associated with a higher risk of developing colorectal cancer.

BRCA1 and BRCA2

BRCA1 and BRCA2 are tumor suppressor genes involved in DNA repair via homologous recombination.
Mutations in BRCA1/BRCA2 are linked to a significantly increased risk of breast, ovarian, and other cancers.
Cells lacking functional BRCA1/BRCA2 proteins are susceptible to chromosomal breaks and aneuploidy.

Carcinogenesis: Accumulation of Mutations

Carcinogenesis typically involves the accumulation of multiple complementary driver mutations in a stepwise fashion over time.
This process is thought to require multiple genetic alterations (e.g., both proto-oncogene activation and tumor suppressor inactivation) before malignant transformation occurs.

Key Points

Knowing the basic concepts of genes and their roles in cellular processes is crucial for understanding cancer development.
Tumor suppressor syndromes are important to consider in patient care and clinical management.
Specific gene alterations are often associated with the development of certain tumors and may serve as diagnostic markers or therapeutic targets.

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Description

Explore the fundamental concepts of genetics, including genes, alleles, and chromosomes, as well as an overview of the cell cycle and its phases. Understand how these foundational principles intertwine with the genetic basis of neoplasia. This quiz will test your knowledge of essential biological processes.