Comparative genomic instabilities of thyroid and colon cancers.

Objectives: To assess the forms and extent of genomic instability in thyroid cancers and colorectal neoplasms and to determine if such measurements could explain the generally excellent prognosis of thyroid malignant neoplasms compared with colon carcinoma.

Design: Tumor genome analyses. Genomic instability was measured by the following 4 methods, listed in ascending order based on the size of events detected: inter-simple sequence repeat polymerase chain reaction (ISSR-PCR), fractional allelic loss (FAL) analysis, array-based comparative genomic hybridization (aCGH), and spectral karyotyping (SKY).

Results: The genomic instability index of 32 thyroid carcinomas, 59 colon carcinomas, and 11 colon polyps was determined by ISSR-PCR; no difference was seen among the 3 groups by this method. Fractional allelic loss rates were comparable in thyroid cancers and colon polyps and lower than FAL rates in colorectal cancers. Indolent papillary thyroid carcinomas were essentially diploid with no large-scale alterations in chromosome number or structure when evaluated by aCGH or SKY. In anaplastic thyroid cancers, aCGH revealed abundant chromosome alterations. Colorectal carcinomas showed extensive copy number changes and chromosomal rearrangements when analyzed by aCGH and SKY.

Conclusions: Genomic alterations in papillary thyroid carcinoma, such as in benign colon polyps, are principally smaller events detected by ISSR-PCR. With the more aggressive tumor types (ie, anaplastic thyroid and colorectal carcinomas), larger events detected by FAL analysis, aCGH, and SKY were revealed. We hypothesize that mutations caused by smaller genomic alterations enable thyroid cells to achieve a minimal malignant phenotype. Mutations for aggressive biological behavior appear with larger genomic events.