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Rearrangements of RET proto-oncogene in papillary thyroid carcinomas
Abstracts
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CHROMOSOME STUDIES IN MEDULLARY AND PAPILLARY THYROID CARCINOMAS AND THEIR BIOLOGICAL CHARACTERIZATION A.Behmel 1, R.Pfragner 2 and G. Wirnsberger 3 t Inst. Med. Biol. and Human Genetics, 2 Inst. Funct. Pathology, 3 Inst. Pathology, University of Graz, AUSTRIA ....
Five apparently sporadic medullary thyroid carcinomas (cell line MTC-SK, SIJ, GER, STAH, EDR) and one papillary thyroid carcinoma (DUA) were characterized through cytogenetic and biological studies (ICC, ISH, Northern blot analysis). ~ thyroid £,.~l.Eg.Ulg..m~: 1990 we reported on continuous cell line M T C - S K : three consistent marker: 46,XX,t(3;10),11p+,22p+. Recently this cell line developed a new clonal marker: t(1q;11p+) SIJ: lymph node metastasis: primary culture: 46,XY,del(6)(p21.1)? From this metastasis a new continuous cell line was established. GER: 47,XY,+7,t(2;18)(p11;p11), constitutional FRA2A. STAH: hypodiploid with random chromosomal loss, two consistent marker chromosomes: der3 (t(3;7)?) and 5p+. EDR: 46,XX,t(1;8)(q25or32.1;p11.1or p21.1). P _ a . i ~ t h v r o i d c a r c i n o m a : D U A : 46,XY,-6,-18,+der6,+der18. None of the breakpoints involve the pericentric region of #10 where the predisposition gene for MTC/MEN2A/MEN2B is localized, in two tumors, however, a deletion 10q11.1 is suspected. MTC - GER and PTC - DUA share breakpoint 18p11. The possible role of the visible structural aberrations in the initiation or progression of the tumors and their correspondence with neuroendocrine markers will be demonstrated.
REARRANGEMENTS OF RET PROTO-ONCOGENE IN PAPILLARY THYROID CARCINOMAS. P. Soares. L. Roque, D. Wynford-Thomas, S. Castedo, J. Soares, M. Sobrinho-Sim6es. Departments of Pathology (PS, MS-S) and Genetics (SC), Medical Faculty, Porto, Portugal. Department of Pathology (LR, JS)-IPOFG-Lisbon, Portugal. Department of Pathology (DWT), University of Wales, College of Medicine, Cardiff, U.K.
Rearrangements of RET proto-oncogene have been reported in papillary thyroid carcinomas, although the proportion of tumors with detectable rearrangements varies considerably between different series. In a series of 13 papillary thyroid carcinomas studied, we found rearrangements of this gene in 2 cases (15%). In both tumors structural chromosomal abnormalities involving band 10qll (where RET proto-oncogene is located) were detected by conventional cytogenetics. Our results confirm the presence of RET rearrangements in a minority of papillary carcinomas. Apart from the possibility that some rearrangements may have been missed by Southern blot analysis, we suggest three explanations for this low incidence: 1) It may be~:that RET activation is simply statistically less likely to occur than alternative (as yet unknown) activating events in this tumor. 2) It may be a relatively late secondary event or, 3) It may reflect the incidence of a hitherto unrecognized sub-population of follicular cells which is uniquely responsive to the biochemical signal provided by the activated RET kinase. Acknowledgments: This work was partly supported by research grants of JNICT and INIC. The probe pPTC was kindly provided by Dr. A Fusco.
13 7
CHROMOSOME STUDIES IN MEDULLARY AND PAPILLARY THYROID CARCINOMAS AND THEIR BIOLOGICAL CHARACTERIZATION A.Behmel 1, R.Pfragner 2 and G. Wirnsberger 3 t Inst. Med. Biol. and Human Genetics, 2 Inst. Funct. Pathology, 3 Inst. Pathology, University of Graz, AUSTRIA ....
Five apparently sporadic medullary thyroid carcinomas (cell line MTC-SK, SIJ, GER, STAH, EDR) and one papillary thyroid carcinoma (DUA) were characterized through cytogenetic and biological studies (ICC, ISH, Northern blot analysis). ~ thyroid £,.~l.Eg.Ulg..m~: 1990 we reported on continuous cell line M T C - S K : three consistent marker: 46,XX,t(3;10),11p+,22p+. Recently this cell line developed a new clonal marker: t(1q;11p+) SIJ: lymph node metastasis: primary culture: 46,XY,del(6)(p21.1)? From this metastasis a new continuous cell line was established. GER: 47,XY,+7,t(2;18)(p11;p11), constitutional FRA2A. STAH: hypodiploid with random chromosomal loss, two consistent marker chromosomes: der3 (t(3;7)?) and 5p+. EDR: 46,XX,t(1;8)(q25or32.1;p11.1or p21.1). P _ a . i ~ t h v r o i d c a r c i n o m a : D U A : 46,XY,-6,-18,+der6,+der18. None of the breakpoints involve the pericentric region of #10 where the predisposition gene for MTC/MEN2A/MEN2B is localized, in two tumors, however, a deletion 10q11.1 is suspected. MTC - GER and PTC - DUA share breakpoint 18p11. The possible role of the visible structural aberrations in the initiation or progression of the tumors and their correspondence with neuroendocrine markers will be demonstrated.
REARRANGEMENTS OF RET PROTO-ONCOGENE IN PAPILLARY THYROID CARCINOMAS. P. Soares. L. Roque, D. Wynford-Thomas, S. Castedo, J. Soares, M. Sobrinho-Sim6es. Departments of Pathology (PS, MS-S) and Genetics (SC), Medical Faculty, Porto, Portugal. Department of Pathology (LR, JS)-IPOFG-Lisbon, Portugal. Department of Pathology (DWT), University of Wales, College of Medicine, Cardiff, U.K.
Rearrangements of RET proto-oncogene have been reported in papillary thyroid carcinomas, although the proportion of tumors with detectable rearrangements varies considerably between different series. In a series of 13 papillary thyroid carcinomas studied, we found rearrangements of this gene in 2 cases (15%). In both tumors structural chromosomal abnormalities involving band 10qll (where RET proto-oncogene is located) were detected by conventional cytogenetics. Our results confirm the presence of RET rearrangements in a minority of papillary carcinomas. Apart from the possibility that some rearrangements may have been missed by Southern blot analysis, we suggest three explanations for this low incidence: 1) It may be~:that RET activation is simply statistically less likely to occur than alternative (as yet unknown) activating events in this tumor. 2) It may be a relatively late secondary event or, 3) It may reflect the incidence of a hitherto unrecognized sub-population of follicular cells which is uniquely responsive to the biochemical signal provided by the activated RET kinase. Acknowledgments: This work was partly supported by research grants of JNICT and INIC. The probe pPTC was kindly provided by Dr. A Fusco.