Initial assessment of a model relating intratumoral genetic heterogeneity to radiological morphology.
Tumour heterogeneity has major implications for tumour development and response to therapy. Tumour heterogeneity results from mutations in the genes responsible for mismatch repair or maintenance of chromosomal stability. Cells with different genetic properties may grow at different rates and exhibit different resistance to therapeutic interventions. To date, there exists no approach to non-invasively assess tumour heterogeneity. Here we present a biologically inspired model of tumour growth, which relates intratumoral genetic heterogeneity to gross morphology visible on radiological images. The model represents the development of a tumour as a set of expanding spheres, each sphere representing a distinct clonal centre, with the sprouting of new spheres corresponding to new clonal centres. Each clonal centre may possess different characteristics relating to genetic composition, growth rate and response to treatment. We present a clinical example for which the model accurately tracks tumour growth and shows the correspondence to genetic variation (as determined by array comparative genomic hybridisation). One clinical implication of our work is that the assessment of heterogeneous tumours using Response Evaluation Criteria In Solid Tumours (RECIST) or volume measurements may not accurately reflect tumour growth, stability or the response to treatment. We believe that this is the first model linking the macro-scale appearance of tumours to their genetic composition. We anticipate that our model will provide a more informative way to assess the response of heterogeneous tumours to treatment, which is of increasing importance with the development of novel targeted anti-cancer treatments.
Noterdaeme
O
O
Department of Engineering Science, University of Oxford, South Parks Road, Oxford OX13PJ, UK. olivier@robots.ox.ac.uk
Kelly
M
M
Friend
P
P
Soonowalla
Z
Z
Steers
G
G
Brady
M
M
D000465:Algorithms; D016880:Anisotropy; D015179:Colorectal Neoplasms; D018450:Disease Progression; D018740:Genetic Heterogeneity; D006801:Humans; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology* / Q000556:secondary / Q000628:therapy; D008954:Models, Biological; D011859:Radiography; D016896:Treatment Outcome
J Neurooncol. 2000 May;48(1):1-12
11026691
Cell. 2006 Dec 1;127(5):905-15
17129778
Semin Oncol. 1989 Apr;16(2):91-105
2652316
J Pathol. 2003 Mar;199(3):345-53
12579536
Nat Biotechnol. 2007 Jun;25(6):675-80
17515910
Nat Genet. 1995 Jan;9(1):48-55
7704024
Genes Chromosomes Cancer. 2005 Nov;44(3):305-19
16075461
Eur J Cancer. 1979 Apr;15(4):383-6
436903
IEEE Trans Med Imaging. 2005 Oct;24(10):1334-46
16229419
J Hepatol. 1998 Jan;28(1):142-9
9537851
Radiology. 2007 Mar;242(3):647-9
17213364
Br J Radiol. 2001 Nov;74(887):983-6
11709461