BIOL 4010 Lecture Notes - Lecture 4: Bernardino Ramazzini, Tumor Suppressor Gene, Cervical Cancer

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champagnemink511

22 Nov 2018

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You can make a connection between genotype and phenotype for oncogenes and tumor suppressors. Oncogenes: gain of function, dominant mutations (one allele) promote carcinogenesis. Tumor suppressor genes: loss of function mutation recessive (loss of function in both alleles) promote oncogenesis. If its overexpression/ hyperactivation is predicted to cause unregulated growth = likely dominant oncogene. If loss of function of gene or product causes unregulated growth = dna repair gene/ tumor suppressor (recessive: by genomic methods, you can also figure out if the mutation on one or 2 alleles. If mutation is on one allele = oncogene (the normal gene is likely to be an activator of a signal transduction path) If both alleles are mutated (recessive) = most likely that it is tumor suppressor = no selective advantage from both alleles (if it is a dominant oncogene) more likely a tumor suppressor or.

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1.) You are studying a particular type of cancer. You observe that the cells are expressing higher than normal levels of the activated version of the G protein Ras (ie, they contain more Ras-GTP than normal).

a.(2 pts) Further study shows that the one of the Ras genes has been mutated, would you classify this as the mutation of a tumor-suppressor gene or an oncogene?

b.(2 pts) Given your knowledge of the regulation of G proteins, suggest an explanation for how this mutant Ras protein results in more Ras-GTP than normal.

c.(2 pts) In a different cancer you also observe an increase in the activated form of Ras, however, in this case, the mutation has occurred in both copies of a gene encoding a protein that normally interacts with Ras. The mutant forms of the protein no longer interact with Ras and this leads to inappropriate growth. Since the mutation leads to cancer, would this loss of function be an example of an oncogene or a tumor-suppressor? Can you suggest a function for this protein?

coffeegerbil810

1. The RAS proteinacquires a mutation that prevents release of GTP. Which of thefollowing characteristics are these cells likely toacquire?

A. Self-Sufficiency in growth signals
B. Insensitivity to anti-growth signals
C. Metastasis

2. Which of the following genes would you suspect to bea tumor supressor?
A. MSH2
B. CDK2
C. c-myc

3. A gene that is involved in a normal cellular processesbut when mutated contribute to cancer developmentis:
A. a proto-oncogene
B. a housekeeping gene

4. When a person carries a mutation in a tumor suppressorgene on one-chromosome and subsequently loses function of theirwildtype tumor suppressor allele, this describes:
A. gene conversion to an oncogene
B. loss of heterozygosity
C. haploinsufficiency

5. The mechanism by which alterations in DNA methylationcould promote carcinogenesis is:
A. by lengthening telomeres
B. by interacting with reactive oxygen species and thereforebecoming a potent mutagen
C. by either repressing or enhacing gene expression

6. When anaylzing a cell you find that it has aninactivating mutation in p53 and a mutation in the VEGF receptorthat makes activation independent of ligand binding. Which of thefollowing hallmarks would you expect the cell toexhibit?
I. self-sufficiency in growth
II. insensitivit to anti-growith signals
III. limitless replicative potential
IV. evading apoptosis
V. sustained angiogenesis

A. IV and V only
B. II, III, VI
C. I and III only

graywalrus182

Use this list of gene elements to answer the following questions: (a) Promoter
(b) Exon
(c) Enhancer

(d) Intron
(e) 5â untranslated region

(f) 3â untranslated region

Problem 1. Which of the above gene elements are transcribed? You may choose more than one answer.

Problem 2. Which of the above gene elements are translated? You may choose more than one answer.

Problem 3. Which of the above gene elements are regulatory? You may choose more than one answer.

Problem 4. Which of the above gene elements are coding? You may choose more than one answer.

Problem 6. A mutation occurs in a gene with the following sequence: AAGCT. An example of a deletion mutation in this sequence would be AACT (loss of G). Using AAGCT as your normal sequence, give an example for the following types of mutations

(a) Insertion (b) Transition

Problem 7. A mutation occurs in the coding region of a gene with the following sequence AAGTGC. The translated sequence is Lysine (AAG), Cysteine (TGC). Give an example of following types of mutation using AAGTGC as your normal sequence. Provide the translated sequence caused by the mutation. (Hint: You will need a codon table to translate the sequence)

(a) Synonymous mutation
(b) Non-synonymous missense mutation

Problem 8. Patient 1 has a tumor causing mutation in a pro-growth gene. The mutated protein allows the cell to grow without receiving growth signals from outside the cell. Is the mutated gene an oncogene or a tumor suppressor? Why? Which hallmark is the gene associated with?

Problem 9. Patient 2 has a tumor which contains a loss of function mutation in the P53 gene. How would you determine if it is a somatic or germ line mutation?

Problem 10. Patient 3 has a tumor causing mutation in a gene called telomerase. The function of telomerase is to lengthen the ends of chromosomes. What hallmark is telomerase associated with? Is the mutation gain of function or loss of function? (Hint: to answer this question, you need to understand which hallmark telomere length is associated with)

BIOL 4010 Lecture Notes - Lecture 4: Bernardino Ramazzini, Tumor Suppressor Gene, Cervical Cancer

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