Screening for genetic aberrations in papillary thyroid cancer using comparative genomic hybridization

Authors


Abstract

Background

Papillary thyroid carcinomas (PTCs) are a heterogenous group of neoplasms that display a wide variability in clinical behaviour. Knowledge of the genetic composition of these tumours may help improve prognostication, but is currently limited. The aim of this study was to identify the genetic composition of pathologically low-risk papillary thyroid cancers and identify differences based on age, using a powerful, genome-wide analytical technique, comparative genomic hybridization (CGH).

Methods

Tumour samples from patients with pathologically confirmed well differentiated PTC, less than 4 cm in size and without extrathyroidal extension or distant metastasis, were procured from the institutional tumour bank. CGH analysis was performed by differentially labelling tumour and normal DNA with fluorescent agents. The labelled DNAs were coprecipitated and simultaneously hybridized to normal metaphase chromosomes on glass slides. After chromosomal segregation, computerized image analysis was performed to detect fluorochrome intensity along the entire length of each chromosome. The ratio of fluorescent signal intensity was used to identify the presence of genetic abnormalities. Statistical age-group comparisons of the CGH findings were performed using Fisher's exact test.

Results

Genetic abnormalities were detected in ten of 21 cases. A recurrent pattern of aberrations was identified, involving losses at chromosomes 1p, 9q, 17, 19 and 22, and gains at 4, 6 and 13. The prevalence of CGH-detectable aberrations was not influenced by age, but loss of chromosome 22 was unique to patients aged less than 40 years (P = 0·05) and was associated with a higher rate of locoregional metastasis (19 versus 80 per cent; P = 0·02).

Conclusion

Two distinct patterns of genetic composition were observed in PTC. One group had no detectable abnormalities, while the other had a recurrent pattern of gains and losses that localized to identical chromosomal loci. Although a divergent pattern of involvement was seen in younger patients, the direct clinical significance of this finding needs to be elucidated. Moreover, the identified pattern of alterations suggests that novel oncologically consequential genes are present within the involved loci. Molecular cloning of the genes at each of these sites is warranted. © 2000 British Journal of Surgery Society Ltd

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