Oncogene Analysis from the Mass - all or part??

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Anonymous
Anonymous Member Posts: 1,376
edited June 2014 in Stage I Breast Cancer

When they do an oncogene analysis, do they use the entire mass - the entire tissue taken or a specimen of the mass?

My report states "60 invasive cancer cells counted" and I am confused by how much tissue or mass they were checking.

Thank you.

Diane

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  • Anonymous
    Anonymous Member Posts: 1,376
    edited April 2012

    bump - hoping someone knows - thanks

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  • voraciousreader
    voraciousreader Member Posts: 7,496
    edited April 2012

     http://www.nejm.org/doi/full/10.1056/NEJMoa1113205

    March 8.2012

    Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing

    Marco Gerlinger, M.D., Andrew J. Rowan, B.Sc., Stuart Horswell, M.Math., James Larkin, M.D., Ph.D., David Endesfelder, Dip.Math., Eva Gronroos, Ph.D., Pierre Martinez, Ph.D., Nicholas Matthews, B.Sc., Aengus Stewart, M.Sc., Patrick Tarpey, Ph.D., Ignacio Varela, Ph.D., Benjamin Phillimore, B.Sc., Sharmin Begum, M.Sc., Neil Q. McDonald, Ph.D., Adam Butler, B.Sc., David Jones, M.Sc., Keiran Raine, M.Sc., Calli Latimer, B.Sc., Claudio R. Santos, Ph.D., Mahrokh Nohadani, H.N.C., Aron C. Eklund, Ph.D., Bradley Spencer-Dene, Ph.D., Graham Clark, B.Sc., Lisa Pickering, M.D., Ph.D., Gordon Stamp, M.D., Martin Gore, M.D., Ph.D., Zoltan Szallasi, M.D., Julian Downward, Ph.D., P. Andrew Futreal, Ph.D., and Charles Swanton, M.D., Ph.D.

    N Engl J Med 2012;  366:883-892March 8, 2012

     

    Background Intratumor heterogeneity may foster tumor evolution and adaptation and hinder personalized-medicine strategies that depend on results from single tumor-biopsy samples.  

    Methods To examine intratumor heterogeneity, we performed exome sequencing, chromosome aberration analysis, and ploidy profiling on multiple spatially separated samples obtained from primary renal carcinomas and associated metastatic sites. We characterized the consequences of intratumor heterogeneity using immunohistochemical analysis, mutation functional analysis, and profiling of messenger RNA expression.  

    Results Phylogenetic reconstruction revealed branched evolutionary tumor growth, with 63 to 69% of all somatic mutations not detectable across every tumor region. Intratumor heterogeneity was observed for a mutation within an autoinhibitory domain of the mammalian target of rapamycin (mTOR) kinase, correlating with S6 and 4EBP phosphorylation in vivo and constitutive activation of mTOR kinase activity in vitro. Mutational intratumor heterogeneity was seen for multiple tumor-suppressor genes converging on loss of function; SETD2, PTEN, and KDM5C underwent multiple distinct and spatially separated inactivating mutations within a single tumor, suggesting convergent phenotypic evolution. Gene-expression signatures of good and poor prognosis were detected in different regions of the same tumor. Allelic composition and ploidy profiling analysis revealed extensive intratumor heterogeneity, with 26 of 30 tumor samples from four tumors harboring divergent allelic-imbalance profiles and with ploidy heterogeneity in two of four tumors.  

    Conclusions Intratumor heterogeneity can lead to underestimation of the tumor genomics landscape portrayed from single tumor-biopsy samples and may present major challenges to personalized-medicine and biomarker development. Intratumor heterogeneity, associated with heterogeneous protein function, may foster tumor adaptation and therapeutic failure through Darwinian selection. (Funded by the Medical Research Council and others.)

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  • voraciousreader
    voraciousreader Member Posts: 7,496
    edited April 2012

    Basically, what they're saying is that they don't look at the entire tumor...only a specimen and that genetic testing may NOT be effective because different parts of the tumor may be more or less aggressive then the sample......

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  • Anonymous
    Anonymous Member Posts: 1,376
    edited April 2012

    Voracious Reader - Thank you - I am glad you were no ton the Titanic btw.  Good info.

    That's what I thought and got from the read.  Thus the FISH test which may make a change in the determination, either way.  

    I was wondering about the fact of so few cancer cells in a 3 cm x 3 cm mass.  Was a little hopeful for a day or two since the path report also stated there was scarring and neucrosis in the mass itself, that most likely from my Rife machine.  

    Thanks for the follow up.  Have added NEJM to bookmarks.

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