4 ms·

Precision Oncology: Epigenetic Patterns Predict Glioblastoma Outcomes

45 points by sciadvance 10y ago

gmarx 10y ago
Makes sense. An interesting question is what causes the epigenetic modifications that drive the tumor forward. Do the driver mutations also cause these modification? Is it random and these cells are selected for?
- epistasis 10y ago
  It's also the other way around: the epigenetic state and physical conformation of the genome drives what subsequent mutations happen. Mina Bissel has been doing great work over the past 30 years showing that many breast "cancer" cell lines lose their cancer phenotype when they're in the proper 3D structures. Mutations are a key part of cancer, but they're not sufficient to be the sole drivers of carcinogenesis.
  - gmarx 10y ago
    You mean when the chromosomes are in their proper structures? What messes up the physical conformation of the chromosomes? Is it a combination of existing mutation and epigenitic mods? Or something else?
kensai 10y ago
Just a reminder: the guidelines for gliomas (brain tumors) have been updated after almost 10 years. And the outcome is more than ever decided at a molecular level. I am pretty sure this kind of information will be included in the next version.
- telchar 10y ago
  Just checking, do you mean "haven't been updated"?
  - epistasis 10y ago
    No, there has been a recent update, the first in 10 years. And genomic tests play a large part in the changes
  - niels_olson 10y ago
    Hi, pathologist here. Keeping up with updates to classification schemes is a non-trivial part of our practice. To the point that many visit the CAP protocols before signing out any malignant case, just to make sure they're going from the most current template. We actually have a lecture on the most recent classification of lymphoid neoplasms tomorrow morning. And we had the second part of the neuro update as a lecture from our neuropathologist last week.
nrau 10y ago
My mother unfortunately passed away from this horrible disease many years ago when I was not yet 10 years old. Even more unfortunate is that life expectancy once one is diagnosed with glioblastoma today is not any longer than it was back then (35 years ago). Patients on average live 8-12 months. It's depressing to see this, and I hope we can make bigger strides in the years ahead.
- WhitneyLand 10y ago
  Looks like it is slightly better now. Standard cases have life expectancy of 2-3 years and very aggressive cases are at 14.6 months. Either way a devastating cancer, sorry you had to go through that. http://www.abta.org/brain-tumor-information/types-of-tumors/glioblastoma.html http://www.abta.org/brain-tumor-information/types-of-tumors/...
apathy 10y ago
Interested to hear how this is "precision oncology". Do the 5hmC patterns predict treatment response? (Spoiler: no, because this was retrospective; need a trial to validate) Do they provide information above and beyond IDH or co-1/19 status? (Spoiler: also no, partly because N=30 instead of over 1,000 in the TCGA LGG/GBM cohort) I would expect this from the PR organs of a major university or other donation-pandering body. I am saddened to see it from Collins, who knows better. The treatments that seem to work in glioblastoma center on dendritic cell vaccines or T-cell priming, at least at this point in time. Radiation is a temporary respite and only succeeds for focal (rather than diffuse) lesions in most cases; furthermore, "success" is relative (very few GBM cases are cured, even in younger patients). So while trials are afoot doing the brutally difficult work of evaluating actual candidates for cures, we're directed towards studies of marks that are almost certainly a proxy for metabolic activity. In bulk cells, natch. Way to go. :-(

45 points by sciadvance 10y ago

gmarx 10y ago

Makes sense. An interesting question is what causes the epigenetic modifications that drive the tumor forward. Do the driver mutations also cause these modification? Is it random and these cells are selected for?

epistasis 10y ago
It's also the other way around: the epigenetic state and physical conformation of the genome drives what subsequent mutations happen. Mina Bissel has been doing great work over the past 30 years showing that many breast "cancer" cell lines lose their cancer phenotype when they're in the proper 3D structures. Mutations are a key part of cancer, but they're not sufficient to be the sole drivers of carcinogenesis.
- gmarx 10y ago
  You mean when the chromosomes are in their proper structures? What messes up the physical conformation of the chromosomes? Is it a combination of existing mutation and epigenitic mods? Or something else?

kensai 10y ago

Just a reminder: the guidelines for gliomas (brain tumors) have been updated after almost 10 years. And the outcome is more than ever decided at a molecular level. I am pretty sure this kind of information will be included in the next version.

telchar 10y ago
Just checking, do you mean "haven't been updated"?
- epistasis 10y ago
  No, there has been a recent update, the first in 10 years. And genomic tests play a large part in the changes
- niels_olson 10y ago
  Hi, pathologist here. Keeping up with updates to classification schemes is a non-trivial part of our practice. To the point that many visit the CAP protocols before signing out any malignant case, just to make sure they're going from the most current template. We actually have a lecture on the most recent classification of lymphoid neoplasms tomorrow morning. And we had the second part of the neuro update as a lecture from our neuropathologist last week.

nrau 10y ago

My mother unfortunately passed away from this horrible disease many years ago when I was not yet 10 years old. Even more unfortunate is that life expectancy once one is diagnosed with glioblastoma today is not any longer than it was back then (35 years ago). Patients on average live 8-12 months. It's depressing to see this, and I hope we can make bigger strides in the years ahead.

WhitneyLand 10y ago
Looks like it is slightly better now. Standard cases have life expectancy of 2-3 years and very aggressive cases are at 14.6 months. Either way a devastating cancer, sorry you had to go through that. http://www.abta.org/brain-tumor-information/types-of-tumors/glioblastoma.html http://www.abta.org/brain-tumor-information/types-of-tumors/...

apathy 10y ago

Interested to hear how this is "precision oncology". Do the 5hmC patterns predict treatment response? (Spoiler: no, because this was retrospective; need a trial to validate) Do they provide information above and beyond IDH or co-1/19 status? (Spoiler: also no, partly because N=30 instead of over 1,000 in the TCGA LGG/GBM cohort) I would expect this from the PR organs of a major university or other donation-pandering body. I am saddened to see it from Collins, who knows better. The treatments that seem to work in glioblastoma center on dendritic cell vaccines or T-cell priming, at least at this point in time. Radiation is a temporary respite and only succeeds for focal (rather than diffuse) lesions in most cases; furthermore, "success" is relative (very few GBM cases are cured, even in younger patients). So while trials are afoot doing the brutally difficult work of evaluating actual candidates for cures, we're directed towards studies of marks that are almost certainly a proxy for metabolic activity. In bulk cells, natch. Way to go. :-(