Podcast Beta
Questions and Answers
Which option best describes a version of a gene?
What term is used to describe tightly packed DNA?
What is the basic building block of DNA?
Which definition best matches the term that contains instructions to make a particular protein?
Signup and view all the answers
Which option describes a structure that has two arms?
Signup and view all the answers
How many chromosomes do most human cells have?
Signup and view all the answers
How many chromatids does a human chromosome usually have following DNA replication?
Signup and view all the answers
Cyclins are proteins that function primarily to regulate which aspect of the cell?
Signup and view all the answers
What primarily determines the fate of a cell in relation to apoptosis?
Signup and view all the answers
What is a common cause of chromosomal translocations that can lead to cancer?
Signup and view all the answers
What is the significance of the Philadelphia chromosome in cancer?
Signup and view all the answers
Which of the following options describes a mechanism of genetic damage that can lead to tumorigenesis?
Signup and view all the answers
Which of the following conditions can lead to the overexpression of Bcl-2, thereby evading apoptosis?
Signup and view all the answers
What is the primary role of oncogenes in cancer cells?
Signup and view all the answers
What mutation is most commonly associated with the BRAF gene in neoplasia?
Signup and view all the answers
Which type of mutation involves the replacement of one nucleotide with another?
Signup and view all the answers
Which of the following best describes the function of telomerase in cancer cells?
Signup and view all the answers
What mechanism do RAS mutations most commonly exemplify?
Signup and view all the answers
How does MYC contribute to cell growth regulation?
Signup and view all the answers
What are the characteristics of oncoproteins compared to their normal counterparts?
Signup and view all the answers
Which statement about the MAPK pathway is correct?
Signup and view all the answers
What is a fundamental role of transmembrane receptors in signal transduction pathways?
Signup and view all the answers
What characterizes driver mutations in the context of neoplasia?
Signup and view all the answers
How do somatic mutations differ from germ cell mutations?
Signup and view all the answers
Which of the following accurately describes genomic alterations?
Signup and view all the answers
What is the outcome when mutations occur in a single precursor cell?
Signup and view all the answers
What cellular functions can be modulated by signal transduction pathways?
Signup and view all the answers
What differentiates passenger mutations from driver mutations?
Signup and view all the answers
Which of the following best describes the impact of mutations on gene expression?
Signup and view all the answers
What is a consequence of mutations in the TP53 tumor suppressor gene?
Signup and view all the answers
What type of DNA damage does Xeroderma pigmentosum primarily affect?
Signup and view all the answers
Which repair mechanism is primarily affected in individuals with Xeroderma pigmentosum?
Signup and view all the answers
What increases the risk of colorectal cancer in Lynch syndrome?
Signup and view all the answers
How much does Xeroderma pigmentosum increase the risk of skin cancers?
Signup and view all the answers
Which of these genes is NOT associated with Lynch syndrome?
Signup and view all the answers
What is the primary function of mismatch repair (MMR) proteins?
Signup and view all the answers
Which types of cancer are individuals with Lynch syndrome at increased risk for?
Signup and view all the answers
Study Notes
Chromosomes, Genes, and Alleles
- APC gene is located at 5q21 on a chromosome
- Allele is a version of a gene
- Chromosome is tightly packed DNA
- Nucleotide is the building block of DNA
- Gene contains instructions to make a protein
- Chromosome has two arms
- Most human cells have 46 chromosomes
- A human chromosome usually has two chromatids
Cell Cycle
- The cell cycle is a series of events that take place in a cell as it prepares for division (grows) and then divides into two daughter cells.
- G0 is the resting phase where the cell spends most of its time
- Cyclins are proteins that turn on kinases
- Kinases are enzymes called cyclin-dependent kinases (CDKs) that increase in activity in response to elevated cyclin levels
- CDK inhibitors, which are chemicals, inhibit CDK function
Signal Transduction Pathways
- Proteins encoded by genes participate in signaling pathways
- Chemical or physical signals are transmitted through a cell as a series of molecular events
- Many genes that are mutated in neoplasia encode proteins that are part of signal transduction pathways
- Transmembrane receptors bind extracellular signaling molecules
- Signal transduction pathways modulate many different cellular functions
From Gene to Signaling Pathway...to Gene
- Mutations in genes that encode proteins participating in signal transduction pathways can change gene expression or activate cell signaling/division independent of external stimuli
Neoplasia is Genetic
- Carcinogenesis is a result of non-lethal genetic damage
- Tumors are formed by clonal expansion of a single precursor cell that experienced genetic damage
- Tumors are clonal
- Genomic alterations may be inherited, arise from environmental influences, or occur stochastically
- Driver alterations contribute to the development of a malignant phenotype
- Passenger alterations are much more frequent than driver alterations but are not relevant to the development of a malignant phenotype
- Carcinogenesis results from the step-wise accumulation of complementary driver mutations over time
- Tumors continue to evolve genomically during outgrowth and progression
Genetic Mutations
- Genetic mutations are permanent changes in the DNA sequence
- Mutations that arise in germ cells (egg, sperm) are transmitted to offspring and can give rise to inherited diseases
- Mutations that arise in somatic cells are important in giving rise to cancers and some congenital malformations
- Mutations interfere with gene expression
Germ and Somatic Cells
- Germ cells have 23 chromosomes
Regulatory Genes and Cancer Causing Mutations
- There are four classes of normal regulatory genes that are the main targets of cancer-causing mutations: proto-oncogenes, tumor suppressor genes, genes that regulate programmed cell death/apoptosis, and genes involved in DNA repair.
Oncogenes
- Oncogenes are mutated proto-oncogenes that promote autonomous cell growth in cancer cells.
- Oncogenes are gain-of-function mutations
- They encode mutant proteins called oncoproteins
- Oncoproteins have gained function to promote cell growth independently of normal extracellular growth-promoting signals
MAPK Pathway Alterations and BRAF Mutations
- The MAPK (mitogen activated protein kinase) pathway is present in 78-88% of ameloblastomas
- BRAF mutations are most common
- BRAFV600E mutations account for 90% of all BRAF mutations seen in neoplasia
- The BRAFV600E mutation results from BRAF c.1799T>A: Thymine (T) is replaced by adenine (A) at coding DNA sequence (nucleotide) 1799, which is a point mutation and activating mutation
- The BRAF protein consists of 766 amino acids
Oncogenic Proteins
- Growth factors
- Growth factor receptors
- Proteins involved in the signaling cascade
- Nuclear regulatory proteins
- Cell cycle regulators
RAS and MYC Mutations
- RAS is the most commonly mutated oncogene
- MYC is an oncogene that activates expression of many genes involved in cell growth
- MYC can reprogram plain somatic cells into pluripotent stem cells
- MYC upregulates telomerase in some contexts
- MYC contributes to stem-cell like immortalization of tumor cells
Telomerase
- Telomerase is an enzyme that lengthens telomeres, which results in limitless replicative potential and contributes to 'cell immortality'
Oncogene Description
- Driver
Evasion of Programmed Cell Death (Apoptosis)
- Apoptosis is programmed cell death in response to pathologic conditions such as carcinogenic mutations
- The Bcl-2 family consists of 25 pro-apoptotic or anti-apoptotic genes
- Relative expression of Bcl-2 family proteins determines cell fate
Follicular Lymphoma evades Cell Death
- Follicular lymphoma has overexpression of Bcl-2 via a chromosomal translocation
- Two-thirds of chromosomal translocations arise from erroneous repair of DNA double-strand breaks
Philadelphia Chromosome
- The Philadelphia chromosome is the most famous translocation, t(9;22), which is characteristic of chronic myelogenous leukemia
Chromosomal Translocation
- Chromosomal translocations are a "shortcut" to cancer
- Mucoepidermoid carcinoma of the hard palate with (11;19) CRTC1-MAML2 translocation is associated with both CRTC1 and MAML2, which are transcription co-activators
Common Mechanisms of Genetic Damage
- Point mutations
- Gene deletions
- Gene amplifications
- Chromosomal translocations
Genomic Instability
- Defects in genes involved in DNA repair are often the source of genomic instability
- Genetic aberrations increase mutation rates which contribute to tumor progression
- TP53 is a tumor suppressor gene that, when mutated, cannot arrest cell division to repair DNA damage or initiate apoptosis in irreversibly damaged cells
- Humans are surrounded by mutagenic environmental agents like sunlight, radiation, and chemicals
- Cancer is a rare outcome of these exposures due to:
- Ability of normal cells to repair DNA damage
- Apoptosis as a protective response
- Normal surveillance mechanisms of the immune system
Xeroderma Pigmentosum
- Xeroderma pigmentosum is a cancer predisposition syndrome where individuals have an impaired ability to repair UV-induced DNA damage
- UV radiation frequently causes abnormal cross-linking of pyrimidine bases
- Normal, error-free DNA replication cannot occur with UV damage
- UV-induced DNA damage is normally repaired by the nucleotide excision repair (NER) system
- The NER system does not work properly in individuals with xeroderma pigmentosum
- Xeroderma pigmentosum is an autosomal recessive syndrome caused by inherited mutations in genes that encode NER proteins
- Individuals with xeroderma pigmentosum have a 1000-fold increased risk of skin cancers, a median age of tumor development of 8 years old, and an increased risk of squamous cell carcinoma of the lower lip and tip of tongue
Hereditary Nonpolyposis Colon Cancer Syndrome (Lynch Syndrome)
- During DNA replication, DNA mismatch repair (MMR) proteins act as "spell-checkers" to detect, excise, and repair defects
- If the MMR protein's proofreading function is lost, genetic mutations are more likely to accumulate and a greater mutational load contributes to the accumulation of complementary driver mutations
- MMR proteins are encoded by MSH2, MLH1, MSH6, PMS2, EPCAM genes
- Germline mutations in these genes:
- Increase risk of colorectal cancer
- Increase the risk of other cancers (endometrium, stomach, brain, skin, etc.)
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Related Documents
Description
This quiz explores the fundamental concepts of chromosomes, genes, and the cell cycle. You'll learn about the structure of DNA, the role of alleles and genes, and the phases of the cell cycle, including important proteins like cyclins and kinases. Test your understanding of these key biological processes!