Abstract
Cytogenetic and molecular analyses of thyroid tumors have indicated that these neoplasms represent a good model for analyzing human epithelial cell multistep carcinogenesis. They comprise, in fact, a broad spectrum of lesions with different phenotypes and variable biological and clinical behavior. Molecular analysis has detected specific genetic alterations in the different types of thyroid tumors. In particular, the well-differentiated carcinomas of the papillary type are characterized by activation of the receptor tyrosine kinases (RTKs), RET and NTRKI proto-oncogenes. Cytogenetic analysis of these tumors has contributed to defining the chromosomal mechanisms leading to RTK ontogenic activation. In the majority of cases, intrachromosomal inversions of chromosome 10 and chromosome 1 led to the formation of RET-derived and NTRKI-derived oncogenes, respectively. Interestingly, molecular analysis of these oncogenes revealed their nature of chimeric fusion proteins all sharing the tyrosine kinase (TK) domains of the respective proto-oncogenes. Moreover, the sequencing of the oncogenic rearrangements led to the identification of a breakpoint cluster region in both RTK proto-oncogenes. Exposure to ionizing radiation is associated with papillary carcinomas and RET activation has been suggested to be related to this event. Conversely, RAS point mutations are frequently observed in tumors with follicular histology and have been associated with metastatic dissemination. Iodide-deficient areas seem to provide a higher frequency of RAS positive follicular carcinomas. Finally, a high prevalence of TP53 point mutations has been detected only in undifferentiated or anaplastic carcinomas and found to correlate inversely with BCL2 expression. All of these findings are contributing to the definition of genetic and environmental factors relevant for the pathogenesis of thyroid tumors. Moreover, the characterization of specific genetic lesions could provide significant molecular tools for a better differential diagnosis and for the development of novel therapeutic avenues for thyroid cancer.
| Original language | English |
|---|---|
| Pages (from-to) | 1-14 |
| Number of pages | 14 |
| Journal | Genes Chromosomes and Cancer |
| Volume | 16 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - May 1996 |
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ASJC Scopus subject areas
- Cancer Research
- Genetics
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Cytogenetics and molecular genetics of carcinomas arising from thyroid epithelial follicular cells. / Pierotti, Marco A.; Bongarzone, Italia; Borrello, Maria Grazia; Greco, Angela; Pilotti, Silvana; Sozzi, Gabriella.
In: Genes Chromosomes and Cancer, Vol. 16, No. 1, 05.1996, p. 1-14.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cytogenetics and molecular genetics of carcinomas arising from thyroid epithelial follicular cells
AU - Pierotti, Marco A.
AU - Bongarzone, Italia
AU - Borrello, Maria Grazia
AU - Greco, Angela
AU - Pilotti, Silvana
AU - Sozzi, Gabriella
PY - 1996/5
Y1 - 1996/5
N2 - Cytogenetic and molecular analyses of thyroid tumors have indicated that these neoplasms represent a good model for analyzing human epithelial cell multistep carcinogenesis. They comprise, in fact, a broad spectrum of lesions with different phenotypes and variable biological and clinical behavior. Molecular analysis has detected specific genetic alterations in the different types of thyroid tumors. In particular, the well-differentiated carcinomas of the papillary type are characterized by activation of the receptor tyrosine kinases (RTKs), RET and NTRKI proto-oncogenes. Cytogenetic analysis of these tumors has contributed to defining the chromosomal mechanisms leading to RTK ontogenic activation. In the majority of cases, intrachromosomal inversions of chromosome 10 and chromosome 1 led to the formation of RET-derived and NTRKI-derived oncogenes, respectively. Interestingly, molecular analysis of these oncogenes revealed their nature of chimeric fusion proteins all sharing the tyrosine kinase (TK) domains of the respective proto-oncogenes. Moreover, the sequencing of the oncogenic rearrangements led to the identification of a breakpoint cluster region in both RTK proto-oncogenes. Exposure to ionizing radiation is associated with papillary carcinomas and RET activation has been suggested to be related to this event. Conversely, RAS point mutations are frequently observed in tumors with follicular histology and have been associated with metastatic dissemination. Iodide-deficient areas seem to provide a higher frequency of RAS positive follicular carcinomas. Finally, a high prevalence of TP53 point mutations has been detected only in undifferentiated or anaplastic carcinomas and found to correlate inversely with BCL2 expression. All of these findings are contributing to the definition of genetic and environmental factors relevant for the pathogenesis of thyroid tumors. Moreover, the characterization of specific genetic lesions could provide significant molecular tools for a better differential diagnosis and for the development of novel therapeutic avenues for thyroid cancer.
AB - Cytogenetic and molecular analyses of thyroid tumors have indicated that these neoplasms represent a good model for analyzing human epithelial cell multistep carcinogenesis. They comprise, in fact, a broad spectrum of lesions with different phenotypes and variable biological and clinical behavior. Molecular analysis has detected specific genetic alterations in the different types of thyroid tumors. In particular, the well-differentiated carcinomas of the papillary type are characterized by activation of the receptor tyrosine kinases (RTKs), RET and NTRKI proto-oncogenes. Cytogenetic analysis of these tumors has contributed to defining the chromosomal mechanisms leading to RTK ontogenic activation. In the majority of cases, intrachromosomal inversions of chromosome 10 and chromosome 1 led to the formation of RET-derived and NTRKI-derived oncogenes, respectively. Interestingly, molecular analysis of these oncogenes revealed their nature of chimeric fusion proteins all sharing the tyrosine kinase (TK) domains of the respective proto-oncogenes. Moreover, the sequencing of the oncogenic rearrangements led to the identification of a breakpoint cluster region in both RTK proto-oncogenes. Exposure to ionizing radiation is associated with papillary carcinomas and RET activation has been suggested to be related to this event. Conversely, RAS point mutations are frequently observed in tumors with follicular histology and have been associated with metastatic dissemination. Iodide-deficient areas seem to provide a higher frequency of RAS positive follicular carcinomas. Finally, a high prevalence of TP53 point mutations has been detected only in undifferentiated or anaplastic carcinomas and found to correlate inversely with BCL2 expression. All of these findings are contributing to the definition of genetic and environmental factors relevant for the pathogenesis of thyroid tumors. Moreover, the characterization of specific genetic lesions could provide significant molecular tools for a better differential diagnosis and for the development of novel therapeutic avenues for thyroid cancer.
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UR - http://www.scopus.com/inward/citedby.url?scp=0029939832&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1098-2264(199605)16:1<1::AID-GCC1>3.0.CO;2-4
DO - 10.1002/(SICI)1098-2264(199605)16:1<1::AID-GCC1>3.0.CO;2-4
M3 - Article
C2 - 9162191
AN - SCOPUS:0029939832
VL - 16
SP - 1
EP - 14
JO - Genes Chromosomes and Cancer
JF - Genes Chromosomes and Cancer
SN - 1045-2257
IS - 1
ER -