Chromosomal Imbalances in Post-Chernobyl Thyroid Tumors

Abstract

Tissue samples from 60 post-Chernobyl childhood thyroid tumors have been investigated. We used comparative genomic hybridization (CGH) to detect chromosomal gains and losses within the tumor DNA. This is the first CGH study on childhood thyroid tumors. The post-Chernobyl tumors showed chromosomal imbalances in 30% of tumors. The most frequent DNA copy number changes in post-Chernobyl tumors involved chromosomes 2, 7q11.2-21, 13q21-22, 21 (DNA gains), and chromosomes 16p/q, 20q, 22q (DNA losses). Some of these specific alterations detected in post-Chernobyl thyroid tumors (deletions on chromosomes 16p/q and 22q) have previously been reported in thyroid tumors as associated with an aggressive biologic behavior and may therefore also account for the more aggressive phenotype of papillary thyroid carcinoma (PTC) found in post- Chernobyl tumors. Eighteen percent of post-Chernobyl PTC that exhibit RET rearrangements also showed chromosomal imbalances indicating that either additional genetic events are involved in this subset of tumors, or that intratumoral genetic heterogeneity exists in these tumors, suggesting a oligoclonal pattern to tumor development.

Chromosomal aberrations in thyroid follicular-cell neoplasia: in the search of novel oncogenes and tumour suppressor genes

“…In a conventional CGH study on radiation-associated PTC the most frequent copy number changes reported were on chromosomes 2, 7q11.2-21, 13q21-22, 16, 20, 21 and 22 (Richter, et al 2004) which was in accordance with the chromosome 22 changes reported in other studies (Hemmer, et al 1999;Singh, et al 2000) linking its presence to a widely invasive subtype of PTC. In addition, Kitamura et al (2000) described an association of allelic losses of 1q, 4p, 9 and 16q with survival in PTC.…”

Array CGH demonstrates characteristic aberration signatures in human papillary thyroid carcinomas governed by RET/PTC

“…To our knowledge, this represents the first array CGH study on PTCs, which includes post-Chernobyl thyroid tumours. We report Finn et al, 2004;Richter et al, 2004). The similarity in the results from conventional and array CGH demonstrates the reliability of the array CGH approach we used.…”

A Radiation-Induced Gene Signature Distinguishes Post-Chernobyl from Sporadic Papillary Thyroid Cancers

“…This is in line with the genotypes of our post-Chernobyl PTC group (Table 1). With comparative genomic hybridization (CGH), chromosomal imbalances were detected in 30% of post-Chernobyl PTC (27). The most frequent changes in DNA copy number involved chromosomes 2, 7, 13, 16 and 21; some of these specific alter- ations have been reported to be associated with aggressive biological behavior (27).…”

“…With comparative genomic hybridization (CGH), chromosomal imbalances were detected in 30% of post-Chernobyl PTC (27). The most frequent changes in DNA copy number involved chromosomes 2, 7, 13, 16 and 21; some of these specific alter- ations have been reported to be associated with aggressive biological behavior (27). A recently published CGH study concluded that, in particular, DNA gains in post-Chernobyl thyroid cancers appeared to be influenced by radiation exposure (28), which should have an impact at the transcription level.…”