Cancer Biology: Signal Transduction & Neoplasia

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What is the primary function of the Bcl-2 family of genes in relation to apoptosis?

To repair DNA damage

To regulate the immune response

To induce cell division

To determine cell fate (correct)

What is a common origin of chromosomal translocations in cancer?

Erroneous repair of DNA double-strand breaks (correct)

Natural aging processes

Infections caused by viruses

Duplications of chromosome segments

Which chromosomal translocation is most closely associated with chronic myelogenous leukemia?

t(11;19)

t(6;14)

t(3;8)

t(9;22) (correct)

What do CRTC1 and MAML2 have in common in the context of certain cancers?

They are both transcription co-activators Signup and view all the answers

Which of the following is NOT a common mechanism of genetic damage leading to cancer?

Chromosomal duplications Signup and view all the answers

What is the most common syndrome associated with colon cancer?

Lynch syndrome Signup and view all the answers

What characteristic is associated with Lynch syndrome colorectal carcinoma?

Microsatellite instability-high (MSI-H) Signup and view all the answers

Which genes are primarily involved in familial breast cancer cases?

BRCA1 and BRCA2 Signup and view all the answers

What type of gene is primarily responsible for promoting cell growth?

Proto-oncogenes Signup and view all the answers

Which process is used by BRCA proteins to repair DNA breaks?

Homologous recombination Signup and view all the answers

Which of the following best defines oncogenes?

Mutated proto-oncogenes that promote cell growth Signup and view all the answers

What is the primary consequence of the BRAFV600E mutation?

Autonomous activation of the MAPK pathway Signup and view all the answers

What role does MYC play in cancer cell biology?

Activates genes that promote cell growth Signup and view all the answers

Which gene is the most commonly mutated oncogene?

RAS Signup and view all the answers

What is considered a key feature of teleomerase in cancer cells?

It contributes to cell immortality Signup and view all the answers

The mutation BRAF c.1799T>A results in which amino acid change?

Valine to Glutamate Signup and view all the answers

Which component is not typically associated with oncogenesis?

Basic metabolic enzymes Signup and view all the answers

How does the MAPK pathway contribute to cancer cell proliferation?

By driving cell proliferation signaling Signup and view all the answers

What is the consequence of a mutation in the TP53 tumor suppressor gene?

Cells can indefinitely continue cell division. Signup and view all the answers

What is the primary role of nucleotide excision repair (NER) in humans?

To repair UV-induced DNA damage. Signup and view all the answers

What is the primary role of transmembrane receptors in signal transduction pathways?

To bind extracellular signaling molecules Signup and view all the answers

What increased risk does a mutation in the genes encoding MMR proteins pose?

Increased risk of colorectal cancer. Signup and view all the answers

Which genetic syndrome is associated with an impaired ability to repair UV-induced DNA damage?

Xeroderma pigmentosum. Signup and view all the answers

What distinguishes driver mutations from passenger mutations in the context of carcinogenesis?

Driver mutations contribute to malignant phenotypes, while passenger mutations do not Signup and view all the answers

Which statement best describes the evolution of tumors?

Tumors evolve genomically during outgrowth and progression Signup and view all the answers

How do environmental agents typically lead to cancer in humans?

Most normal cells can repair DNA damage. Signup and view all the answers

What type of damage is commonly caused by UV radiation in DNA?

Cross-linking of pyrimidine bases. Signup and view all the answers

How are mutations that arise in somatic cells characterized?

They contribute to cancers and some congenital malformations Signup and view all the answers

What is the median age for tumor development in individuals with Xeroderma pigmentosum?

8 years. Signup and view all the answers

What effect do mutations generally have on gene expression?

They may interfere with gene expression Signup and view all the answers

Which of the following genes is NOT associated with hereditary nonpolyposis colon cancer syndrome?

TP53. Signup and view all the answers

What is a key characteristic of neoplasia in relation to genetic damage?

It results from non-lethal genetic damage Signup and view all the answers

In what type of cells do mutations that lead to hereditary diseases occur?

Germ cells only Signup and view all the answers

What is the consequence of mutations in genes encoding proteins in signal transduction pathways?

They can change gene expression or activate cell signaling independently of external stimuli Signup and view all the answers

Study Notes

Signal Transduction Pathways

Signal transduction pathways regulate cellular activity, such as division, gene expression and metabolism.
The pathway begins with an extracellular signaling molecule binding to a transmembrane receptor, such as a receptor tyrosine kinase or a g protein-coupled receptor.
The receptor initiation triggers a cascading interaction of intracellular proteins, ultimately reaching the nucleus to modify cellular functions in response to the signal.

Genetic Basis of Neoplasia

Cancer arises from mutations that alter genes involved in cell growth, survival and genomic stability.
Neoplasia results from non-lethal genetic damage, leading to clonal expansion of a single precursor cell that has experienced genetic damage.
Genomic alterations can be inherited, caused by environmental influences, or occur stochastically.
Driver mutations contribute directly to cancer development, while passenger mutations are more common but do not drive the malignant phenotype.
Tumors continue to evolve genetically during growth and progression, accumulating additional mutations.

Genetic Mutations and Cell Function

Genetic mutations are permanent changes in the DNA sequence.
Mutations in germ cells are inherited by offspring, potentially causing hereditary diseases.
Mutations in somatic cells can give rise to cancer and some congenital malformations, but do not cause hereditary diseases.
Mutations can interfere with gene expression, leading to altered protein function.
Germ cells have 23 chromosomes.

Genes Targeted by Cancer-Causing Mutations

Oncogenes are mutated proto-oncogenes, promoting autonomous cell growth.
Tumor suppressor genes normally inhibit cell growth but lose their function when mutated.
Several genes regulate programmed cell death or apoptosis, contributing to tumor survival.
Genes involved in DNA repair are essential for maintaining genomic stability, mutations in these genes can lead to increased mutation rates and cancer progression.

Oncogenes

Oncogenes promote cell growth by participating in signaling pathways that drive cell proliferation.
They are mutant versions of proto-oncogenes, acquiring a gain-of-function mutation that allows them to promote cell growth independently of normal external stimuli.
The most commonly mutated oncogene is RAS.
MYC is an oncogene that activates genes involved in cell growth, reprogramming cells into pluripotent stem-like cells, upregulating telomerase, and contributing to immortalization of tumor cells.
Telomerase is an enzyme that lengthens telomeres, contributing to limitless replication potential and cellular immortality.
MAPK pathway alterations are present in 78-88% of ameloblastomas.

BRAF Mutations: A Primary Oncogenic Driver

BRAF mutations commonly occur in cancer, particularly BRAFV600E, accounting for 90% of all BRAF mutations.
This mutation substitutes glutamate for valine at codon 600, causing a point mutation in DNA sequence 1799.
The BRAFV600E mutation represents an activating mutation of the BRAF protein, resulting in constitutive activation of the MAPK pathway.
BRAF protein consists of 766 amino acids.

Evasion of Apoptosis in Cancer

Apoptosis, or programmed cell death, is a crucial mechanism to eliminate damaged or unwanted cells.
Cancer cells often evade apoptosis, allowing them to persist and proliferate despite mutations.
The Bcl-2 family of proteins plays a critical role in regulating apoptosis, with pro-apoptotic and anti-apoptotic members.
Relative expression of these Bcl-2 family proteins sets the balance between cell survival and cell death.

Follicular Lymphoma: A Model of Apoptosis Evasion

Follicular lymphoma exhibits overexpression of the anti-apoptotic protein Bcl-2 due to chromosomal translocation.
Chromosomal translocations are genetic rearrangements where a chromosome segment is transferred to another chromosome.
These translocations often arise from erroneous repair of DNA double-strand breaks.

Chromosomal Translocations: Shortcut to Cancer

The Philadelphia chromosome, a hallmark of chronic myelogenous leukemia (CML), results from a t(9;22) translocation.
Translocations can lead to the fusion of genes, creating aberrant proteins that contribute to cancer development.
For example, the CRTC1-MAML2 translocation in mucoepidermoid carcinoma of the hard palate involves two transcription co-activators.

Mechanisms of Genetic Damage

Point mutations involve changes in a single base pair of DNA.
Gene deletions remove a portion of a gene.
Gene amplifications lead to an increased copy number of a gene.
Chromosomal translocations result in the exchange or relocation of genetic material between chromosomes.

Genomic Instability: A Hallmark of Cancer

Genomic instability refers to increased rates of mutations within the genome, accelerating cancer progression.
Defects in DNA repair genes contribute to genomic instability.
The TP53 tumor suppressor gene, when mutated, cannot arrest cell division to repair DNA damage or initiate apoptosis in damaged cells, leading to unchecked proliferation.

Environmental Mutagens: Exposure and Repair

Humans are exposed to various environmental mutagens, including sunlight, radiation, and chemicals.
Cancer is a relatively rare outcome of these exposures due to efficient DNA repair mechanisms, apoptotic pathways, and immune surveillance.

Xeroderma Pigmentosum: A Defective DNA Repair Syndrome

Xeroderma pigmentosum (XP) is an autosomal recessive disorder characterized by severely impaired UV-induced DNA damage repair.
XP patients exhibit a lack of proper nucleotide excision repair (NER), the major pathway for removing UV-induced lesions.
This deficiency results in a high accumulation of unrepaired DNA damage, leading to a dramatically increased risk of skin cancers, often developing in early childhood.

Hereditary Nonpolyposis Colon Cancer (Lynch Syndrome): A Mismatch Repair Deficiency

Lynch syndrome, also known as hereditary nonpolyposis colon cancer, is caused by mutations in DNA mismatch repair (MMR) genes.
MMR proteins function as ‘spell-checkers’ during DNA replication, detecting and repairing base pair insertions or deletions.
Mutations in MMR genes lead to a higher rate of mutations, increasing the risk of colorectal cancer and other cancers like endometrial, stomach, brain, and skin cancers.

MMR and Microsatellite Instability

Lynch syndrome colorectal carcinomas often exhibit microsatellite instability (MSI), characterized by increased mutation rates in repetitive DNA sequences.
Microsatellite instability can affect gene expression and protein function, often leading to frameshift mutations.

BRCA Genes and Familial Breast Cancer

BRCA1 and BRCA2 are tumor suppressor genes involved in DNA repair through a process called homologous recombination.
Mutations in BRCA genes increase the risk of breast, ovarian, and other cancers.
Cells lacking functional BRCA proteins develop chromosomal breaks and aneuploidy, leading to uncontrolled growth and tumor formation.
10-15% of breast cancers are hereditary and BRCA1 or BRCA2 are mutated in 25% of familial cases.

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Description

Explore the intricate processes of signal transduction pathways and their role in regulating cellular functions. This quiz delves into the genetic basis of neoplasia, examining how mutations lead to cancer development and progression. Test your knowledge on the mechanisms behind cellular signaling and cancer genetics.