Changes to Pathology

In the recent JAMA there is an interesting discussion regarding the treatment of biopsy samples. The issue is simple and critical. Typically the pathologist examines the tissue sample using a variety of techniques and reaches a conclusion. However with the advances in genomics one would like to examine the gene and pathway micro structure of the sample. They state:   

Genomics is poised to revolutionize cancer treatment. Whole genome sequencing is becoming more rapid, accurate, and affordable, and the ability to use genomic data to match biologically based therapy to an individual is becoming a reality. As the sequencing endeavor transitions from a heroic effort performed by a dedicated team for a particular patient to a routine component of most, if not all, cancer diagnoses, standards for acquiring appropriate tissue samples also must evolve. This is necessary because an individual's native (germline) genome must be compared with the genome of the tumor.

They then continue:   

Gerlinger et al reported an analysis of whole exome sequencing of frozen tissue from multiple regions of tumors among patients with metastatic renal cell carcinoma. The most salient finding was intratumor diversity, whereby driver mutations in the mTOR gene were found only in some regions of the tumors. The authors concluded that single tumor biopsies may “underestimate the tumor genomics landscape” and “may present major challenges to personalized medicine and biomarker development." Here, the implication is particularly striking because many needle biopsies and aspirations performed routinely today have barely adequate tissue to be regarded as fulfilling an ideal “single” sample, let alone enough to detect intratumor heterogeneity.

The issue is significant for many reasons. Having the germline and the somatic profiles we can start to see where changes go. But I believe that there are more issues:

1. Stem cell: If indeed we have stem cells and they are somewhat rare then we need a large selection of cells to compare.

2. Metastasis: If we have mets then we need to compare the in situ cells to the mets, and perhaps across many such mets to see what changes where. This may be especially true for such things as the miR-26a microRNA local environment discussion made recently.

3. miRNA: What about the miRNAs, these must also be tracked.

This opens a set of truly critical issues. Collecting cells is important, enough cells is critical, and establishing a data base and access to it is essential. Clearly a new set of tools will be needed but this open a vast array of new data usages which we need.