5 ms·

One of the things I am hoping for is a general database of cancers and the mutations they exhibit. By putting them in a database, we may be able to treat based

by jamra 9y ago

One of the things I am hoping for is a general database of cancers and the mutations they exhibit. By putting them in a database, we may be able to treat based off the mutation instead of the locality in the body. When my mother was diagnosed with ovarian cancer, she was given chemo therapy for ovarian cancer that was unrelated to hers in everything but location. Since her cancer was very rare, there was no real study that could have helped. If we start keeping a database, it may help us find new treatments and stop giving dying people ineffective poisons.

xyhopguy 9y ago
Those already exist! TCGA for starters..
- nonbel 9y ago
  Interesting, even the highlighted research on that page is about copy number rather than point mutations, indels, etc, being important: https://cancergenome.nih.gov/newsevents/newsannouncements/sarcoma_2017 https://cancergenome.nih.gov/newsevents/newsannouncements/sa...
  - dekhn 9y ago
    turns out, genomicists have very little idea how the real world works, and they're still arguing over these kinds of things, rather than working out the underlying mechanistic details.
  - xyhopguy 9y ago
    My (weak) understanding is that the functional impact of a mutation is more important than the type of variations. Otherwise we would see recurrent point mutations rather than hotspots right? FWIW though, people have already been able to predict treatment outcome from mutation profile. Turns out the hard part is picking up on mutations present in only a tiny subset of the tumor.
    - sungam 9y ago
      We do see recurrent point mutations as well as recurrently mutated pathways.
    - nonbel 9y ago
      I was thinking about Peter Duesberg. He has been really pushing the aneuploidy idea for a few decades now, but everyone ignores him since he is a "denier": http://www.newsweek.com/can-hiv-denying-scientist-cure-cancer-81157 http://www.newsweek.com/can-hiv-denying-scientist-cure-cance... It'd be pretty funny if he turned out to be correct.
      - xyhopguy 9y ago
        I don't really know any history about cancer research, but as long as I've been in genomics people have talked about it. Difficulty is actually finding CNVs. These days it's not so hard. It's also important to remember that we know some cancers (leukemia for instance) are diploid and rarely develop anueploidy.
dekhn 9y ago
Such databases exist, and they have helped a little, but they barely justify the investment, so far. cancer mutations are a complex thing. It's not as simple as: linear function(vector_of_mutations) -> perfect diagnosis of cancer type.
- jamra 9y ago
  That’s true. I’m well aware of this. I downloaded a few of these databases and tried to match my moms results in exactly the way you mention. I couldn’t get the vector of mutations from the lab. Perhaps these databases would be more useful if drug companies were allowed to put new drugs forward faster.
- sungam 9y ago
  Interestingly it is exactly this problem I am working on!
  - TeMPOraL 9y ago
    Tell us more!
zaphod12 9y ago
This sort of story is becoming increasingly common, but the good news is that there are a ton of tests in the works and more coming every day: https://www.mskcc.org/msk-impact https://www.mskcc.org/msk-impact Right now it's a complement to the traditional surgical pathology route, and only about 70% accurate, but when surg path and molecular differ, it means extra steps are taken to confirm and hopefully get it absolutely right.
adrianm 9y ago
I am actually in such a database (MSK-IMPACT), so they definitely exist. Check it out here: http://www.cbioportal.org/study?id=msk_impact_2017#summary http://www.cbioportal.org/study?id=msk_impact_2017#summary
iskander 9y ago
There are several such databases, the largest of which is TCGA (https://cancergenome.nih.gov/ https://cancergenome.nih.gov/). They have sequenced >32k patients across several dozen cancer types. Here's their getting started guide: https://docs.gdc.cancer.gov/Data_Portal/Users_Guide/Getting_Started/ https://docs.gdc.cancer.gov/Data_Portal/Users_Guide/Getting_...
bsmrea 9y ago
Here are a few mutation databases, in addition to the ones already mentioned: http://cancer.sanger.ac.uk/cosmic http://cancer.sanger.ac.uk/cosmic https://dcc.icgc.org/ https://dcc.icgc.org/
fossuser 9y ago
I agree - I think the way you 'cure' cancer is probably by doing this. 1. Understand the handful of oncagenes and their mutations that lead to cancer. 2. Sequence every patient's cancer 3. Work on finding drugs like herceptin that nullify the mutations exhibited by the patient. 4. Craft drug cocktails tailored to the patients specific mutations. 5. (In future) - edit the mutation code directly with something like CRISPR.
- ABCLAW 9y ago
  Even if each of these steps was economically viable (which they aren't), this still wouldn't cure cancer. Diagnostic and screening advances are so useful because plenty of these cancers and cancer related disorders run subclinically, and many of them cause lasting systemic damage even after the rogue cell population is decimated. Certainly helpful, but not the end of the fight.
psychometry 9y ago
This is already done. Pan-cancer hotspot mutations identified through targeted panel sequencing inform treatment.
ABCLAW 9y ago
I'm curious; what do you mean by database of cancers? If you mean actual tissue-banks with specific cancerous samples isolated and identified for testing, then they exist. If you mean just databases of genomic data related to cancers, those exist too, but sadly you can't just BLAST away every problem you find. Tissue is extremely limited. The volume required to do testing shreds through the volume of tissue removed during biopsy very quickly, leaving limited amounts left over for study. As a result, access to cancerous tissue samples is actually a tremendous limiter on this type of research. In a company I worked on prior which was developing analogous technology, our ability to access a number of university affiliated tissue banks was a key differentiation between us and the competition.
sjg007 9y ago
Sorry to hear about your mom. Ovarian cancer is one of the worst because it usually has no symptoms until it is very advanced. For any cancer, early detection is the key. That's when surgery, chemo and radiation are most likely to be most effective. So I think this is where these blood tests will have the largest impact.
- killjoywashere 9y ago
  Any cancer large enough to shed detectable amounts of DNA into the blood stream is quite a ways along. You want to detect the pre-malignant when it's a few millimeters in size. Which is hard enough on your skin, let alone an internal organ.

by jamra 9y ago

xyhopguy 9y ago

Those already exist! TCGA for starters..

nonbel 9y ago
Interesting, even the highlighted research on that page is about copy number rather than point mutations, indels, etc, being important: https://cancergenome.nih.gov/newsevents/newsannouncements/sarcoma_2017 https://cancergenome.nih.gov/newsevents/newsannouncements/sa...
- dekhn 9y ago
  turns out, genomicists have very little idea how the real world works, and they're still arguing over these kinds of things, rather than working out the underlying mechanistic details.
- xyhopguy 9y ago
  My (weak) understanding is that the functional impact of a mutation is more important than the type of variations. Otherwise we would see recurrent point mutations rather than hotspots right? FWIW though, people have already been able to predict treatment outcome from mutation profile. Turns out the hard part is picking up on mutations present in only a tiny subset of the tumor.
  - sungam 9y ago
    We do see recurrent point mutations as well as recurrently mutated pathways.
  - nonbel 9y ago
    I was thinking about Peter Duesberg. He has been really pushing the aneuploidy idea for a few decades now, but everyone ignores him since he is a "denier": http://www.newsweek.com/can-hiv-denying-scientist-cure-cancer-81157 http://www.newsweek.com/can-hiv-denying-scientist-cure-cance... It'd be pretty funny if he turned out to be correct.
    - xyhopguy 9y ago
      I don't really know any history about cancer research, but as long as I've been in genomics people have talked about it. Difficulty is actually finding CNVs. These days it's not so hard. It's also important to remember that we know some cancers (leukemia for instance) are diploid and rarely develop anueploidy.

dekhn 9y ago

Such databases exist, and they have helped a little, but they barely justify the investment, so far. cancer mutations are a complex thing. It's not as simple as: linear function(vector_of_mutations) -> perfect diagnosis of cancer type.

jamra 9y ago
That’s true. I’m well aware of this. I downloaded a few of these databases and tried to match my moms results in exactly the way you mention. I couldn’t get the vector of mutations from the lab. Perhaps these databases would be more useful if drug companies were allowed to put new drugs forward faster.
sungam 9y ago
Interestingly it is exactly this problem I am working on!
- TeMPOraL 9y ago
  Tell us more!

zaphod12 9y ago

This sort of story is becoming increasingly common, but the good news is that there are a ton of tests in the works and more coming every day: https://www.mskcc.org/msk-impact https://www.mskcc.org/msk-impact Right now it's a complement to the traditional surgical pathology route, and only about 70% accurate, but when surg path and molecular differ, it means extra steps are taken to confirm and hopefully get it absolutely right.

adrianm 9y ago

I am actually in such a database (MSK-IMPACT), so they definitely exist. Check it out here: http://www.cbioportal.org/study?id=msk_impact_2017#summary http://www.cbioportal.org/study?id=msk_impact_2017#summary

iskander 9y ago

There are several such databases, the largest of which is TCGA (https://cancergenome.nih.gov/ https://cancergenome.nih.gov/). They have sequenced >32k patients across several dozen cancer types. Here's their getting started guide: https://docs.gdc.cancer.gov/Data_Portal/Users_Guide/Getting_Started/ https://docs.gdc.cancer.gov/Data_Portal/Users_Guide/Getting_...

bsmrea 9y ago

Here are a few mutation databases, in addition to the ones already mentioned: http://cancer.sanger.ac.uk/cosmic http://cancer.sanger.ac.uk/cosmic https://dcc.icgc.org/ https://dcc.icgc.org/

fossuser 9y ago

I agree - I think the way you 'cure' cancer is probably by doing this. 1. Understand the handful of oncagenes and their mutations that lead to cancer. 2. Sequence every patient's cancer 3. Work on finding drugs like herceptin that nullify the mutations exhibited by the patient. 4. Craft drug cocktails tailored to the patients specific mutations. 5. (In future) - edit the mutation code directly with something like CRISPR.

ABCLAW 9y ago
Even if each of these steps was economically viable (which they aren't), this still wouldn't cure cancer. Diagnostic and screening advances are so useful because plenty of these cancers and cancer related disorders run subclinically, and many of them cause lasting systemic damage even after the rogue cell population is decimated. Certainly helpful, but not the end of the fight.

psychometry 9y ago

This is already done. Pan-cancer hotspot mutations identified through targeted panel sequencing inform treatment.

ABCLAW 9y ago

I'm curious; what do you mean by database of cancers? If you mean actual tissue-banks with specific cancerous samples isolated and identified for testing, then they exist. If you mean just databases of genomic data related to cancers, those exist too, but sadly you can't just BLAST away every problem you find. Tissue is extremely limited. The volume required to do testing shreds through the volume of tissue removed during biopsy very quickly, leaving limited amounts left over for study. As a result, access to cancerous tissue samples is actually a tremendous limiter on this type of research. In a company I worked on prior which was developing analogous technology, our ability to access a number of university affiliated tissue banks was a key differentiation between us and the competition.

sjg007 9y ago

Sorry to hear about your mom. Ovarian cancer is one of the worst because it usually has no symptoms until it is very advanced. For any cancer, early detection is the key. That's when surgery, chemo and radiation are most likely to be most effective. So I think this is where these blood tests will have the largest impact.

killjoywashere 9y ago
Any cancer large enough to shed detectable amounts of DNA into the blood stream is quite a ways along. You want to detect the pre-malignant when it's a few millimeters in size. Which is hard enough on your skin, let alone an internal organ.