Results of a study in this week’s issue of THE LANCET suggest that an imbalance in specific genetic material on chromosomes 8 and 18 could be a better predictor of colorectal cancer prognosis than conventional histopathological assessment.
Chromosome imbalances occur in many cancers and represent important biological properties of tumours. However, measurements of such imbalances are difficult. Previous research has suggested that imbalances on specific areas of chromosomes 8 and 18 could prevent the action of tumour-suppressor genes and lead to poor disease prognosis. Bert Vogelstein and colleagues from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, USA, Wei Zhou from Emory University School of Medicine, Atlanta, USA, and colleagues used a new, quantitative approach to investigate the prognostic value of chromosome imbalances in early-stage colorectal cancers.
180 patients with localised colorectal cancer (ie, with no evidence of lymph-node or distant metastases) were studied at the time of surgery. DNA from tumours was tested for genetic imbalances on the shorter part of chromosome 8 (8p) and on the longer part of chromosome 18 (18q) by digital SNP (single-nucleotide polymorphism); a technique in which each allele (half the component of a single gene) in a sample is directly counted. Surviving patients had an average follow-up of around five and a half years, and disease recurrence was used as the clinical endpoint.
Tumours were divided into three groups: “L” tumours (93 patients) had allelic imbalances of chromosomes 8p and 18q, “L/R” tumours (60 patients) had allelic imbalances of either chromosome 8p or 18q but not both, and “R” tumours (27 patients) retained allelic balance for both chromosomes. 5-year disease-free survival was 100% for patients with R tumours, 74% for patients with L/R tumours, and 58% for those with L tumours.
In an accompanying Commentary (p 183), Garth Anderson and Bruce Brenner from Roswell Park Cancer Institute, Buffalo, NY, USA, conclude: “The long-term potential of genome-based markers for cancers is tremendous. As the genetic events giving rise to such tumours become defined, exploitation of markers for use as diagnostic and prognostic tools must continue to be a focus, because surgical resection can remove even the most heterogeneous tumour cell population if it is detected early. Patients with an increased risk of recurrence despite adequate surgery who may benefit from adjuvant therapies can also be identified. Those genes in particular whose loss influences the progress and course of the tumour by reducing overall genomic stability may prove most valuable as markers; the relevant genes on 8p and 18q, once identified and confirmed, may fall into this category.”
Contact: Professor Bert Vogelstein, Department of Oncology, School of Medicine, Johns Hopkins University, 1650 Orleans Street, CRB, Suite 589, Baltimore MD 21231, USA; T) +1 410 955 8878; F) +1 410 955 0548; E) vogelbe@welch.jhu.edu
Dr Garth Anderson, Departments of Cancer Genetics and Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA; T) +1 716 845 8233; F) +1 716 845 1698; E) garth.anderson@roswellpark.org
Journal
The Lancet