ASSESSING GENETIC-MARKERS OF TUMOR PROGRESSION IN THE CONTEXT OF INTRATUMOR HETEROGENEITY

This is a report from the Kananaskis working group on quantitative met hods in tumour heterogeneity, Tumour progression is currently believed to result from genetic instability and consequent acquisition of new genetic properties in some of the tumour cells, Cross-sectional assess ment of genetic markers for human tumours requires quantifiable measur es of intratumour heterogeneity for each parameter or characteristic o bserved; the relevance of heterogeneity to tumour progression can best be ascertained by repeated assessment along a tumour progressional ti me Line, This paper outlines experimental and analytic considerations that, with repeated use, should lead to a better understanding of tumo ur heterogeneity, and hence, to improvements in patient diagnosis and therapy, Four general principles were agreed upon at the Symposium: (1 ) the concept of heterogeneity requires a quantifiable definition so t hat it can be assessed repeatably; (2) the quantification of heterogen eity is necessary so that testable hypotheses may be formulated and ch ecked to determine the degree of support from observed data; (3) it is necessary to consider (a) what is being measured, (b) what is current ly measurable, and (c) what should be measured; and (4) the proposal o f working models is a useful step that will assist our understanding o f the origins and significance of heterogeneity in tumours. The proper ties of these models should then be studied so that hypotheses may be refined and validated. (C) 1998 Wiley-Liss, Inc.