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jayanta
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medicine-ONCOLOLY
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07.10.08 (2 months ago)
#1
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MOST COMMMON GENETIC MUTATION IN CANCERS-
1.p 53.
2.HPC.
3.PTEN.
4. Rb GENE.
ANSWER GIVEN IS Rb GENE,BUT I THINK IT SHOULD BE p 53.
AM I ROGHT?
THANKX FRIENDS.
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jayanta
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07.15.08 (2 months ago)
#2
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PLEAASE FRIENDS.
COME ON.
REGARDS.
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drjanak
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Oncogene Mutation
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07.17.08 (2 months ago)
#3
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Genetics – a Conceptual Approach 2002 Benjamin Pierce
Advanced Topics in Genetics: Developmental Genetics, Immunogenetics, and Cancer Genetics
About 75% of colorectal cancers have mutations in tumor-suppressor gene p53, and many also have a mutation in the ras protooncogene. Families with adenomatous polyposis coli carry a defect in a gene called APC, and mutations in APC are found in the cells of tumors that arise sporadically (in persons
without a family history). Additional genes that are frequently mutated in colorectal cancer include the oncogenes myc and neu and the tumor-suppressor gene HNPCC.
Color Atlas of Genetic 3rd Ed – Thieme > Origins of Cancer
Somaticmutations in the p53 gene occur in about half of all tumors.
Germline mutations of p53
Germline mutations of p53 lead to a familial form of multiple different cancers, the autosomal dominant Li–Fraumeni syndrome (MIM 114480) described described in 1969 by Li and Fraumeni in families with individuals affected with diverse types of tumors, mainly soft-tissue sarcomas, early onset breast cancer, brain cancers, cancer of the bone (osteosarcoma) and bone marrow (leukemias), and carcinoma of the lung, pancreas, and adrenal cortex.
Retinoblastoma (MIM 180200) is the most frequent malignant tumor of the eye in infancy and early childhood, with an incidence of about 1 in 15000–25000 live births. It results from loss of function of both alleles of the retinoblastoma gene, RB1. The main types of mutation in hereditary
retinoblastoma are deletions (~26%), insertions (~9%), and point mutations (~65%), including splice-site mutations, distributed relatively evenly along the gene.
Robbins and Cotran PATHOLOGIC BASIS OF DISEASE 7th Ed Ch 7 Neoplasia
Molecular Basis of Cancer
Transcriptional activation of p21 is under the control of p53, a tumor suppressor gene that is mutated in a large proportion of human cancers. The main role of p53 in the cell cycle is one of surveillance, triggering checkpoint controls that slow down or stop cell-cycle progression of damaged cells, or causes apoptosis.
The RAS Oncogene.
The RAS proteins were discovered as products of viral oncogenes. Point mutation of RAS family genes is the single most common abnormality of dominant oncogenes in human tumors. Approximately 15% to 20% of all human tumors contain mutated versions of RAS proteinsWith respect to the second question (i.e., why the loss of RB is not more common in human tumors), the answer is much simpler: Mutations in other genes that control RB phosphorylation can mimic the effect of RB loss, and such genes are mutated in many cancers that may have normal RB genes. Thus, for example, mutational activation of cyclin D or CDK4 would favor cell proliferation by facilitating RB phosphorylation.
In cells that harbor mutations in any one of these other genes, the function of RB is disrupted even if the RB gene itself is not mutated.
General & Systemic Pathology 4th Ed – J.C.E.Underwood
Carcinogenesis & Neoplasia > Genetic Mechanisms in Carcinogenesis
The tumour suppressor gene p53, situated on the short arm of chromosome 17, is the most frequently mutated and extensively studied in human cancer.
Table 11-11. Tumour suppressor genes: functional categories and tumour associations
(Difficult to get the table posted here, but it mentions that p53 mutated in 50% of human cancers; RB1 often mutated in other cancers, APC often mutated in colorectal cancers.
hence RB1 does not seem to mutate as often as p53. Your guess is correct. Go with it.
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The_Druid
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07.17.08 (2 months ago)
#4
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i'll second what drjanak says. p53 is without doubt the most commonly mutated gene in cancers.
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jayanta
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07.20.08 (2 months ago)
#5
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THANKX A LOT DRUID.
REGARDS.
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jayanta
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07.20.08 (2 months ago)
#6
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THANKX JANAK DEAR ONCE AGAIN.
BUT HERE IN KOLKATA AMONG THE STUDENTS THERE IS A LOT OF CONFUSION REGARDING THE ANSWER.
EVEN PROFESSORS ARE NOT SURE.SO, THANK U ONCE AGAIN FOR ANSWERING SUCH AN EASY LOOKING ODD QUESTION.
REGARDS.
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drjanak
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Oncogene Mututation
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07.21.08 (2 months ago)
#7
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21/07/2008
Dear Jayantha,
I have always tried to back up any answer with a reference from a standard text book.
At times I have realized that the answer is at variance from standard medical practice or it pertains to a theory or use which has long since been abandoned. Unfortunately the examiner is still stuck to an old theory or is quizzing you with a different text book in hand.
Hence even the most blatantly correct answer maybe marked wrong by the examiner because the book he has referred to for framing the question, gives a different perspective.
Hence answering any MCQ requires indepth knowledge of the text books and a large degree of luck that you have referred to the correct one.
In life you will find that in any case coming to a conclusion regarding the correct diagnosis or treatment for any patient is usually a lot of common sense, experience and again a large dose of luck.
So I wont be surprised if any of the answers I have given are proven wrong using a different source or different perspective.
But once you have a particular answer, stick to it until proven wrong.
All the best
Dr Janak
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The_Druid
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07.21.08 (2 months ago)
#8
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Well said dr. janak. very wise....
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jayanta
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07.22.08 (2 months ago)
#9
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ABSOLUTELY RIGHT YOU ARE DR. JANAK.
BUT THE WAY YOU HAVE REFERRED THINGS ONE SHOULD EXPECT THAT ANSWERS ARE DEFINITELY RIGHT.
HOPE THE EXAMINERS ARE STUDYING THE LATEST BOOKS.
REGARDS.
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