Abstract
The nuclear disaster that occurred in Chernobyl in 1986 offered the unique opportunity to study the molecular genetics of one human tumor type, papillary carcinoma of the thyroid gland, associated with a specific etiology. We have analyzed RET rearrangements in post-Chernobyl papillary thyroid carcinomas (n = 29), follicular thyroid adenomas (n = 2), and follicular thyroid carcinoma (n = 1) by interphase fluorescence in situ hybridization (FISH) analysis on paraffin-embedded tissue sections. Paraffin sections were microdissected before use to ensure that only tumor was present. Cell nuclei were scored for the presence of a split FISH signal (separated red and green signal) in addition to an overlapping signal. Only cells with either two overlapping signals or one split and one overlapping signal were counted to ensure that only complete cell nuclei had been scored. In total, 23 of 32 cases (72%) showed RET rearrangements diagnosed by FISH interphase analysis. In all cases, the tumors were composed of a mixture of cells with and without ret rearrangement on FISH. In some cases, this distribution was clearly nonrandom because clustering of rearranged cells was detected within the same tumor nodule. Accordingly, only 31% of the cases positive for rearrangement on FISH also scored positive using RT-PCR. These findings suggest that because RET/PTC rear-rangements are not present in a majority of tumor cells, either a fraction of post-Chernobyl papillary thyroid tumors are of multiclonal origin, or ret rearrangement is a later, subclonal event.
| Original language | English |
|---|---|
| Pages (from-to) | 4272-4279 |
| Number of pages | 8 |
| Journal | Journal of Clinical Endocrinology and Metabolism |
| Volume | 89 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Sep 2004 |
Fingerprint
ASJC Scopus subject areas
- Biochemistry
- Endocrinology, Diabetes and Metabolism
Cite this
Heterogeneity in the distribution of RET/PTC rearrangements within individual post-chernobyl papillary thyroid carcinomas. / Unger, Kristian; Zitzelsberger, Horst; Salvatore, Giuliana; Santoro, Massimo; Bogdanova, Tatjana; Braselmann, Herbert; Kastner, Peter; Zurnadzhy, Lyudmilla; Tronko, Nikolay; Hutzler, Peter; Thomas, Gerry.
In: Journal of Clinical Endocrinology and Metabolism, Vol. 89, No. 9, 09.2004, p. 4272-4279.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Heterogeneity in the distribution of RET/PTC rearrangements within individual post-chernobyl papillary thyroid carcinomas
AU - Unger, Kristian
AU - Zitzelsberger, Horst
AU - Salvatore, Giuliana
AU - Santoro, Massimo
AU - Bogdanova, Tatjana
AU - Braselmann, Herbert
AU - Kastner, Peter
AU - Zurnadzhy, Lyudmilla
AU - Tronko, Nikolay
AU - Hutzler, Peter
AU - Thomas, Gerry
PY - 2004/9
Y1 - 2004/9
N2 - The nuclear disaster that occurred in Chernobyl in 1986 offered the unique opportunity to study the molecular genetics of one human tumor type, papillary carcinoma of the thyroid gland, associated with a specific etiology. We have analyzed RET rearrangements in post-Chernobyl papillary thyroid carcinomas (n = 29), follicular thyroid adenomas (n = 2), and follicular thyroid carcinoma (n = 1) by interphase fluorescence in situ hybridization (FISH) analysis on paraffin-embedded tissue sections. Paraffin sections were microdissected before use to ensure that only tumor was present. Cell nuclei were scored for the presence of a split FISH signal (separated red and green signal) in addition to an overlapping signal. Only cells with either two overlapping signals or one split and one overlapping signal were counted to ensure that only complete cell nuclei had been scored. In total, 23 of 32 cases (72%) showed RET rearrangements diagnosed by FISH interphase analysis. In all cases, the tumors were composed of a mixture of cells with and without ret rearrangement on FISH. In some cases, this distribution was clearly nonrandom because clustering of rearranged cells was detected within the same tumor nodule. Accordingly, only 31% of the cases positive for rearrangement on FISH also scored positive using RT-PCR. These findings suggest that because RET/PTC rear-rangements are not present in a majority of tumor cells, either a fraction of post-Chernobyl papillary thyroid tumors are of multiclonal origin, or ret rearrangement is a later, subclonal event.
AB - The nuclear disaster that occurred in Chernobyl in 1986 offered the unique opportunity to study the molecular genetics of one human tumor type, papillary carcinoma of the thyroid gland, associated with a specific etiology. We have analyzed RET rearrangements in post-Chernobyl papillary thyroid carcinomas (n = 29), follicular thyroid adenomas (n = 2), and follicular thyroid carcinoma (n = 1) by interphase fluorescence in situ hybridization (FISH) analysis on paraffin-embedded tissue sections. Paraffin sections were microdissected before use to ensure that only tumor was present. Cell nuclei were scored for the presence of a split FISH signal (separated red and green signal) in addition to an overlapping signal. Only cells with either two overlapping signals or one split and one overlapping signal were counted to ensure that only complete cell nuclei had been scored. In total, 23 of 32 cases (72%) showed RET rearrangements diagnosed by FISH interphase analysis. In all cases, the tumors were composed of a mixture of cells with and without ret rearrangement on FISH. In some cases, this distribution was clearly nonrandom because clustering of rearranged cells was detected within the same tumor nodule. Accordingly, only 31% of the cases positive for rearrangement on FISH also scored positive using RT-PCR. These findings suggest that because RET/PTC rear-rangements are not present in a majority of tumor cells, either a fraction of post-Chernobyl papillary thyroid tumors are of multiclonal origin, or ret rearrangement is a later, subclonal event.
UR - http://www.scopus.com/inward/record.url?scp=4544365901&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4544365901&partnerID=8YFLogxK
U2 - 10.1210/jc.2003-031870
DO - 10.1210/jc.2003-031870
M3 - Article
C2 - 15356021
AN - SCOPUS:4544365901
VL - 89
SP - 4272
EP - 4279
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 9
ER -