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  #1  
Old 09-07-2012
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Question gain of function mutation

A 55 yr old female comes to a hospital for radiotherapy of thyroid cancer for which she diagnosed 1 yr back......her present complaints also include melena and constipation...1yr back she attained menopause(confirmed by FSH levels).....she also states her brother diagnosed with pancreatic cancer 2 yrs back and died.....on examination....her thyroid hormone levels are normal,her Hb - 6.8%..pulse-68/min.....physician on further genetic testing confirms her family deals with the mutations in increased expression of gain of function mutation genes...the activation of the gene physician explaining most likely caused by ?

a) activated tyrosine kinase
b) DNA direct damage due to radiation
c) adenylyl cyclase
d) binding to ATP
e) binding to GTP
f) cyclin dependant kinases
g) zinc finger motifs
h) beta catenin degradation
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Old 09-07-2012
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Default Ras mutation??

Eee..GTP binding protein
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Old 09-07-2012
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Question

2Q) related to the same case above.....the target of the gain of function gene explained above is similar to the target of...?

a) WT1
B) P53
C) Wnt
D) C-MYC
E) NF
F) BRCA-1
G) APC
H) Rb
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  #4  
Old 09-08-2012
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1st question: E.
2nd question: C. Random guess, I believe ras affects 'signal transduction'. What's the answer?

PS. Great question, as always!! Post exp. soon, thanks!
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Old 09-08-2012
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1) a
2) h

Good question. My guess, the patient has Colon cancer, which is hereditary nonpolyposis colorectal cancer. It is due to a mutation of DNA mismatch repair gene.

Looking forward to explanation!
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Old 09-08-2012
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whats the answer?
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Old 09-08-2012
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Correct Answer

1Q) the correct answer is E) binding to GTP
carcinomas of thyroid,colon,pancreas are aasociated with ras protooncogenes(gain of function) mutations......
it has intrinsic GTPase activity so it binds to GDP when in inactive state and phosphorylates by binding to GTP..mutation lead to over expression of ras gene leading to unregulation of cell cycle..

protooncogenes mechanism------1)by activated tyrosine kinases-----a)growth factor receptors - ex---erb-b1-HER2/NEU(breast cancer)
b)signal transduction by binding to a factor-----RET(MEN 2A.2B)

2)by signal transduction (not by tyrosine kinase receptors)-----a) binding to GTP(ras) ;Wnt pathway-bound to beta catenin complex and control it

b) nonreceptor tyrosine kinases----ex--abl(CML)

3)using nuclear transcription factors---like zn finger motifs----ex--MYC(burkitt's lymphoma)

4) by regulating cell cycles-----cyclin dependant kinases(serine/threonine kinases)-----ex--cyclin D activation in mantle cell lymphoma


2Q) the most appropriate answer is E) NF
neurofibromin gene(NF) has a region with intrinsic GTPase activity,.which also signal transduce via binding to GTP and regulate the ras protooncogene by deactivating ras by binding it to GDP....
although the mechanism of Wnt pathway is similar to ras pathway..their targets are different...Wnt will act via signal transduction and bing to beta catenin complex

tumor suppressor genes mechanisms--------
1) using cell surface molecules----- TGF beta activation lead to inhibition of CDK ex-----colon carcinoma

2) signal transduction----NF1( via GTPse activity and binding)--neurofiromatosis

3)beta catenin degradation ---APC gene--cause FAP

4) by regulating nuclear transcription factors
------Rb gene(retinoblastoma).WT-1( wilms tumor)

5) DNA damage by radiation, sunlight-----P53---lifraumeni syndrome ; BRCA1,2--breast cancer,ovarian cancer
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Old 09-09-2012
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Default Correct answer!

Every good question you can see in your real exam, and it is from USMLERx Qb.
The answer is
a) activated tyrosine kinase
The dx is MEN II which is his relation with ret an oncogen that encodes a putative tyrosine kinase receptor
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Old 09-09-2012
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Post

Quote:
Originally Posted by alfjof View Post
Every good question you can see in your real exam, and it is from USMLERx Qb.
The answer is
a) activated tyrosine kinase
The dx is MEN II which is his relation with ret an oncogen that encodes a putative tyrosine kinase receptor
sorry to obey you ....
but how can you diagnose it as MEN 2...when no signs of pheochromocytoma or parathyroid tumors(calcium level) is given.......would there be pancreatic cancer too....?...
and so for medullary thyroid carcinoma,,,would there be radiation as treatment option..
and this is not copied from USMLE Rx....i framed the question .....

but if there is any explanation diagnosing it as MEN 2 then please explain it,,,correct me...
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Old 09-14-2012
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Quote:
Originally Posted by venky2600 View Post
sorry to obey you ....
but how can you diagnose it as MEN 2...when no signs of pheochromocytoma or parathyroid tumors(calcium level) is given.......would there be pancreatic cancer too....?...
and so for medullary thyroid carcinoma,,,would there be radiation as treatment option..
and this is not copied from USMLE Rx....i framed the question .....

but if there is any explanation diagnosing it as MEN 2 then please explain it,,,correct me...
Remember that Oncogenes are genes that induce tumor cell formation. In other words Gain of function results in cancer, requires only 1 damaged allele. An example of an Oncogene is the RET gene, its product is Tyrosine Kinase.

Activation mutations of the RET-proto oncogen are strongly a/w medullary thyroid cancer.

RET proto-oncogen --> Medullary Thyroid Cancer

others:
RAS muations --> Follicular thyroid cancer & follicular adenomas
p53 mutations --> Anaplastic thyroid cancer

Source:
FA 2011, pg. 227

A bit of cross-over, but if you look at FA 2011, pg. 294 in the Endocrine chapter you'll see that tyrosine-kinase pathways are a/w Insuline, IGF-1, FGF, PDGF, GH, prolactin

any such mutation that rev's up tyrosine kinase would cause these hormones to be more active
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Old 09-14-2012
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Quote:
Originally Posted by Ergo Proxy View Post
Remember that Oncogenes are genes that induce tumor cell formation. In other words Gain of function results in cancer, requires only 1 damaged allele. An example of an Oncogene is the RET gene, its product is Tyrosine Kinase.

Activation mutations of the RET-proto oncogen are strongly a/w medullary thyroid cancer.

RET proto-oncogen --> Medullary Thyroid Cancer

others:
RAS muations --> Follicular thyroid cancer & follicular adenomas
p53 mutations --> Anaplastic thyroid cancer

Source:
FA 2011, pg. 227

A bit of cross-over, but if you look at FA 2011, pg. 294 in the Endocrine chapter you'll see that tyrosine-kinase pathways are a/w Insuline, IGF-1, FGF, PDGF, GH, prolactin

any such mutation that rev's up tyrosine kinase would cause these hormones to be more active
thanks for your valuable explanation....but :sorry:the question has nothing to do with RET oncogene.......it's RAS mutation causing thyroid,colon, and pancreatic cancer...
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