Premium
High‐resolution analysis of alterations in medullary thyroid carcinoma genomes
Author(s) -
Flicker Karin,
Ulz Peter,
Höger Harald,
Zeitlhofer Petra,
Haas Oskar A.,
Behmel Annemarie,
Buchinger Wolfgang,
Scheuba Christian,
Niederle Bruno,
Pfragner Roswitha,
Speicher Michael R.
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.26494
Subject(s) - comparative genomic hybridization , carcinogenesis , biology , cancer research , thyroid carcinoma , copy number variation , mutation , pathology , thyroid , cancer , genetics , genome , medicine , gene
Hereditary and sporadic medullary thyroid carcinoma (MTC) are closely associated with RET proto‐oncogene mutations. However, the role of additional changes in the tumor genomes remains unclear. Our objective was the identification of chromosomal regions involved in MTC tumorigenesis and to assess their significance by using MTC‐derived cell lines. We used array‐CGH (comparative genomic hybridization) to map chromosomal imbalances in 52 primary tumors and ten metastases. Eleven tumors (11/52, 21%) were hereditary and 41 (41/52, 79%) were sporadic. Among the latter, 15 tumors (15/41, 37%) harbored RET mutations. Furthermore, we characterized five MTC cell lines in detail and evaluated the tumorigenicity by severe combined immunodeficiency (SCID)‐mouse experiments. Most MTCs had only few copy number changes, and losses of chromosomes 1p, 4q, 19p and 22q were observed most frequently. The number of chromosomal aberrations increased in metastases. Twenty‐three percent (12/52) of the primary tumors did not even show any chromosomal gains and losses. We injected three cell lines (two of these were without chromosomal changes and pathogenic RET mutations) into immune deficient SCID mice, and in each case, we observed rapid tumor growth at the injection sites. Our data suggest that MTCs—in contrast to most other tumor entities—do not acquire a multitude of genomic imbalances. SCID mouse experiments performed with chromosomally normal cell lines and without RET mutations suggest that presently unknown submicroscopic genomic changes are sufficient in MTC tumorigenesis.