Glioblastoma multiforme (GBM) is the most commonand aggressive form of brain cancer in humans.Without any treatment, the mean survival rate is aboutthree months. Even with standard treatments such assurgical resection, radiation, and chemotherapy, themean survival rate is between seven and 14 months.GBM tumors differ in their spectrum of geneticchanges, and these changes may influence the effectof particular treatments. Answer the following questions about the relevance of particular mutations toparticular treatments and outcomes.a. Biopsies of about 20% of GBMs show the expression of a certain mutational variant of the EGFR(epidermal growth factor receptor) protein calledEGFRvIII. The same cancerous cells of theseGBMs also show the expression of normal, wildtype EGFR. Is the gene encoding EGFR a tumorsuppressor gene or a proto-oncogene?b. It is very difficult to induce cells expressingEGFRvIII to undergo apoptosis. If you werea radiologist treating a patient with a GBMthat expresses EGFRvIII, would you usea higher or lower dose of X-rays than withpatients having GBMs with normal EGFRproteins?c. EGFR is a protein that extends through the cellmembrane, with an N-terminal extracellular part(amino acids 1–500) that binds epidermal growthfactor (EGF) and an intracellular C-terminal kinasepart (amino acids 501–1000) that is normallyactivated when EGF binds to EGFR. The activekinase phosphorylates (adds phosphate groups to)other proteins, setting off a signal transductioncascade that promotes cell growth and division.EGFRvIII is a deletion that removes aminoacids 6 through 273 of the EGFR protein.How might this mutant protein contributeto cancer?d. IressaTM is a drug that blocks the kinase activity ofEGFR. Would you expect IressaTM to be a potentialtreatment for GBMs expressing EGFRvIII, orwould you instead anticipate the drug would makethe tumors grow faster?e. Cisplatin is a platinum compound that binds toDNA and damages it, eventually leading to celldeath. ERCC1 is a gene that encodes a DNA repairprotein. GBMs are found that show much higherlevels of transcription of ERCC1 than normal.Would you treat patients having such GBMs withhigher or lower doses of cisplatin than patientswhose tumors have normal amounts of ERCC1mRNAs?
Glioblastoma multiforme (GBM) is the most common
and aggressive form of brain cancer in humans.
Without any treatment, the mean survival rate is about
three months. Even with standard treatments such as
surgical resection, radiation, and chemotherapy, the
mean survival rate is between seven and 14 months.
GBM tumors differ in their spectrum of genetic
changes, and these changes may influence the effect
of particular treatments. Answer the following questions about the relevance of particular mutations to
particular treatments and outcomes.
a. Biopsies of about 20% of GBMs show the expression of a certain mutational variant of the EGFR
(epidermal growth factor receptor) protein called
EGFRvIII. The same cancerous cells of these
GBMs also show the expression of normal, wildtype EGFR. Is the gene encoding EGFR a tumorsuppressor gene or a proto-oncogene?
b. It is very difficult to induce cells expressing
EGFRvIII to undergo apoptosis. If you were
a radiologist treating a patient with a GBM
that expresses EGFRvIII, would you use
a higher or lower dose of X-rays than with
patients having GBMs with normal EGFR
proteins?
c. EGFR is a protein that extends through the cell
membrane, with an N-terminal extracellular part
(amino acids 1–500) that binds epidermal growth
factor (EGF) and an intracellular C-terminal kinase
part (amino acids 501–1000) that is normally
activated when EGF binds to EGFR. The active
kinase phosphorylates (adds phosphate groups to)
other proteins, setting off a signal transduction
cascade that promotes cell growth and division.
EGFRvIII is a deletion that removes amino
acids 6 through 273 of the EGFR protein.
How might this mutant protein contribute
to cancer?
d. IressaTM is a drug that blocks the kinase activity of
EGFR. Would you expect IressaTM to be a potential
treatment for GBMs expressing EGFRvIII, or
would you instead anticipate the drug would make
the tumors grow faster?
e. Cisplatin is a platinum compound that binds to
DNA and damages it, eventually leading to cell
death. ERCC1 is a gene that encodes a DNA repair
protein. GBMs are found that show much higher
levels of transcription of ERCC1 than normal.
Would you treat patients having such GBMs with
higher or lower doses of cisplatin than patients
whose tumors have normal amounts of ERCC1
mRNAs?
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