A241: Genomics and histopathology of tumours, a translational challenge

Leon P Bignold1

1University of Adelaide, Adelaide, SA, Australia

Presenting date: Monday 2 November
Presenting time: 12.20-13.10


Much is known of the genomic abnormalities, and their biological significances, in tumours. However, clinico-pathological assessments of cases of tumors rely on nineteenth century concepts such as of 'differentation' and 'anaplasia' (1). As established inn the 1960s (2), a translational challenge is to analyse the histopathologic abnormalties in tumour cells according to genetic concepts especially sets of phenotypic changes, and explain them using the principles of current genomics.


The genomic disturbances in tumour cells are divided into (i) fixed lesions - e.g  uninucleotide errors and larger lesions such as deletions and amplifications, as well as (ii) progresssive accumulations of lesions ('genomic instabilities') - of nucleotide sequences (mutator phenotype) and well as of larger lesions (karyotypic instability).

The histopathologic abnormalities are approached taking into account the individuality of the histopathological types; (i) each type exhibits a distinct set of phenotypic changes in the parent kind of cell of origin, and (ii) the individual phenotypic changes are variably different among cases of the same tumour type.


It is suggested that (i) each tumour type / set of phenotypic changes depends on genomic events in one, or possibly more, complex loci in the genome. Each complex locus is tumourigenic when mutant only in the particular kind of parent cell in which the tumour type arises. The linkage of particular sets of phenotypic changes to particular kinds of parent cells probably involves a relationship of the complex loci to genes which are active only in the particular kind of parent cell.

(ii) The variabilities in expressions of histopathological abnormalities between cases of the same type of tumour may depend on variable morphisms of effect of the tumourigenic mutational events in the different kinds of orginal parent cells.

(iii) Other variabilities, such as progression from 'benign' to 'malignant' may depend on the development of the different kinds of genomic instabilities (see above).



Established principles of genomic abnormalities in tumour cells may be able to explain the histopathological features of tumours, if these features are approached according to principles of genetics (3).