Experts crack cancer 'gene codes'

[S.A.M.]

US scientists have cracked the entire genetic code of breast and colon cancers, offering new treatment hopes.

The genetic map shows that nearly 200 mutated genes, most previously unknown, help tumours emerge, grow and spread.

The discovery could also lead to better ways to diagnose cancer in its early, most treatable stages, and personalised treatments, Science magazine reports.

Each individual tumour appeared to have a different genetic blueprint, which could explain why cancers can behave very differently from person to person, the scientists said.

"Most of the cancer genes identified in this study have not been previously linked to cancer.

"These newly identified genes could provide rich hunting grounds for scientists looking for new ways of treating or detecting cancers.

http://news.bbc.co.uk/2/hi/health/5325206.stm

Great stuff.

 

[spuriousmonkey]

Read it. It doesn't really say much on how they did it. Hence I will not get excited.

I assume they did a microarray.

 

[S.A.M.]

Read it. It doesn't really say much on how they did it. Hence I will not get excited.

I assume they did a microarray.

I'll try to get the original Science paper from the library later.

 

[S.A.M.]

I wonder what the frequency of "false positives" might be.

Mutations are hardly rare and a tumor cell may contain a lot of genes with mutations that are not directly linked to the tumor progression.

What do you think ?

 

[spuriousmonkey]

Never mind. I have electronic access:

haha...30 authors on the paper.

The elucidation of the human genome sequence has made it possible to identify genetic alterations in cancers in unprecedented detail. To begin a systematic analysis of such alterations, we determined the sequence of well-annotated human protein-coding genes in two common tumor types. Analysis of 13,023 genes in 11 breast and 11 colorectal cancers revealed that individual tumors accumulate an average of 90 mutant genes but that only a subset of these contribute to the neoplastic process. Using stringent criteria to delineate this subset, we identified 189 genes (average of 11 per tumor) that were mutated at significant frequency. The vast majority of these genes were not known to be genetically altered in tumors and are predicted to affect a wide range of cellular functions, including transcription, adhesion, and invasion. These data define the genetic landscape of two human cancer types, provide new targets for diagnostic and therapeutic intervention, and open fertile avenues for basic research in tumor biology.

The initial step toward achieving these goals was the development of methods for high-throughput identification of somatic mutations in cancers. These methods included those for primer design, polymerase chain reaction (PCR), sequencing, and mutational analysis (Fig. 1). The first component involved extraction of all protein-coding sequences from the CCDS genes. A total of 120,839 nonredundant exons and adjacent intronic sequences were obtained from 14,661 different transcripts in CCDS. These sequences were used to design primers for PCR amplification and sequencing of exons and adjacent splice sites.

Eleven cell lines or xenografts of each tumor type (breast and colorectal carcinomas) were used in the discovery screen (table S2, A and B). Two matching normal samples were used as controls to help identify normal sequence variations and amplicon-specific sequencing artifacts such as those associated with GC-rich regions. A total of 3 million PCR products were generated and directly sequenced, resulting in 465 Mb of tumor sequence.

well,... I will not calculate how much money went through that lab for this paper.

 

[S.A.M.]

Here's the methodology:
Science 8 September 2006:
Vol. 313. no. 5792, p. 1370
DOI: 10.1126/science.313.5792.1370

To conduct this mini-cancer-genome project, a 29-person team, headed by Vogelstein and Hopkins colleagues Kenneth Kinzler and Victor Velculescu, began with a database of 13,023 genes that are considered the best-studied and annotated of the 21,000 known genes in the human genome. Led by postdoc Tobias Sjöblom, the team resequenced the protein-coding regions of the genes in 11 breast cancer samples and 11 colon cancer samples, yielding 800,000-plus possible mutations. The team then winnowed out more than 99% of the mutations by removing errors, normal variants, and changes that didn't alter a protein.

edit: looks like you got the research paper

 

[Pete]

Each individual tumour appeared to have a different genetic blueprint, which could explain why cancers can behave very differently from person to person, the scientists said.

This is interesting. I wonder if we'll end up witha new taxonomy of cancers, based on genetic blueprint rather than the location of the cancer.

That would seem to make more sense, right?

Maybe we'll have "Cancer EH178A awareness month" instead of "Breast cancer awareness month".

 

[Theoryofrelativity]

I wonder what the frequency of "false positives" might be.

Mutations are hardly rare and a tumor cell may contain a lot of genes with mutations that are not directly linked to the tumor progression.

What do you think ?

I would think frequent

my consultant (gynae) said that someone (evil scientist) diagnosed something like 500 women with positive smear results then left them to see what happened, apparrantly a significant number became 'normal' again over time while some went on to develop cancer. Bit vague I know I'll try to find a source to clarify. But he was basically telling me that having a positive smear did not necc mean cancer even in the most extreme of cases.

How many people for example develop cancerous tumours and have them 'disappear' without them ever knowing, as they sometimes do after diagnosis. We can never know.

Unless we do random testing and suddenly find we have more 'cancer' cases than existing statistics show as being proportionate with the population.

 

[valich]

Don't get too excited. You are extending these results into other domains, such as pathology and the causative agents. We have a lot of new research that shows that many forms of cancer are caused by viruses.

scientists have cracked the entire genetic code of breast and colon cancers, offering new treatment hopes. The genetic map shows that nearly 200 mutated genes, most previously unknown, help tumours emerge, grow and spread.

This may perhaps show the result: not the cause or pathology!

The mutated genes in breast and colon cancers were almost completely distinct, suggesting very different pathways for the development of each of these cancer types. Each individual tumour appeared to have a different genetic blueprint, which could explain why cancers can behave very differently from person to person.

Again, the results suggest many different pathologies and causes. This is much like stating we know a person died because we found this-and-that, but we still have no idea of how the person acquired cancer, or how he died. Similarly, there is not suggestion in this article that they know the pathologies or the causes. Therefore, what of interest does this article tell us, except as a possible clue so that we can now look backwards towards the causes?

 

[Pete]

How do viruses cause cancer? I'll need a dumbed-down version.

I think I have a fuzzy idea about how viruses work in general - they link to receptors on the cell wall, penetrate the wall in some way, and inject a strand of genetic material.
The injected material then replicates, using the the cell's organelles in some way? This replication eventually leads to cell death, and the release of all the replicated viruses, right?

So where does the cancer come in? Do some infected cells suffer changes to their nuclear DNA, causing them to replicate uncontrollably?

 

[S.A.M.]

How do viruses cause cancer? I'll need a dumbed-down version.

I think I have a fuzzy idea about how viruses work in general - they link to receptors on the cell wall, penetrate the wall in some way, and inject a strand of genetic material.
The injected material then replicates, using the the cell's organelles in some way? This replication eventually leads to cell death, and the release of all the replicated viruses, right?

So where does the cancer come in? Do some infected cells suffer changes to their nuclear DNA, causing them to replicate uncontrollably?

There are two kinds of tumor viruses

DNA tumor viruses
RNA tumor viruses or retroviruses

What they do is basically integrate their genome with the cell and hijack the restraints that are present in normal proliferating cells. Of course, not all of them integrate with the cell, some of them use other mechanisms.

The resultant changes lead to a transformation of the host cells and confer on it properties leading to neoplasia (ability to infiltrate tissue, etc)

The part of the viral genome that codes for cancer is called an oncogene. Oncogenes can take over the cell cycle machinery, producing proteins (e.g. T antigens) and cause the cell to become immortal (among other things) and hence result in a tumor

[Viral oncogenes have human homologues (called proto oncogenes) which are normally expressed at low levels. They may however get activated under certain circumstances e.g. by a carcinogen and are implicated in non-virally induced cancers]

The simplest example of a DNA virus is the Pappilomaviruses or those which cause warts.

RNA viruses or retroviruses are similar except that they need to copy the RNA into DNA (in the cell) before they can function.


There are six distinct families of tumor viruses.

http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=cooper.section.2622