Low-level genomic instability is a feature of papillary thyroid carcinoma: an array comparative genomic hybridization study of laser capture microdissected papillary thyroid carcinoma tumors and clonal cell lines.

Abstract

CONTEXT:

Previous chromosomal comparative genomic hybridization (CGH) studies of papillary thyroid carcinoma (PTC) have demonstrated a low prevalence of aberrations, with the majority of tumors showing no evidence of chromosomal instability. The technique of CGH can be optimized, however, using array CGH and laser capture microdissection to ensure pure cell populations for analysis.

OBJECTIVE:

To assess PTC using array CGH applied to laser capture microdissected tumor cells and pure cell cultures.

DESIGN:

Well-characterized PTC (known ret/PTC and BRAF mutation status), including samples from 5 tumors with classic morphology, 3 follicular variant tumors, and 3 clonal PTC cell lines, were analyzed.

RESULTS:

Copy gain and loss occurred in all of the tumor cases and cell lines examined. The most common recurrent aberrations involved gains on chromosomes 1, 5, 7, 11, 15, 17, and 22, with recurrent deletions occurring on chromosomes 4, 18, and 19. Analysis of the data from the 8 tumor samples showed that amplifications of TP73 (1p36.33), SNRPN (15q12), and PDGFB (22q13.1) occurred exclusively in tumors with a wild type BRAF.

CONCLUSIONS:

This study shows a higher prevalence of aberrations detected using array CGH allied to laser capture microdissection than previously described in the literature, and it appears that the combination of laser capture microdissection and arrayed clones optimizes studies utilizing CGH. Copy gain of PDGFB occurs in a subset of tumors showing no evidence of mutated BRAF or rearranged ret, suggesting that copy gain of PDGFB may underlie the increased expression of platelet-derived growth factor described recently in the literature.

• Authors: Stephen Finn, Paul Smyth, Esther O'Regan, Suzanne Cahill, Mary Toner, Conrad Timon, Richard Flavin, John O'Leary, Orla Sheils
• Journal: Archives of pathology & laboratory medicine (Arch Pathol Lab Med) Vol. 131 Issue 1 Pg. 65-73 (Jan 2007) ISSN: 1543-2165 [Electronic] United States
• PMID: 17227125 (Publication Type: Journal Article)

Chemical References

• Autoantigens
• DNA, Neoplasm
• DNA-Binding Proteins
• Nuclear Proteins
• Proto-Oncogene Proteins c-sis
• Ribonucleoproteins, Small Nuclear
• SNRPN protein, human
• Tumor Suppressor Proteins
• snRNP Core Proteins
• Proto-Oncogene Proteins c-ret
• RET protein, human
• BRAF protein, human
• Proto-Oncogene Proteins B-raf

Topics

• Adult
• Aged
• Autoantigens (genetics)
• Carcinoma, Papillary (genetics, pathology)
• Cell Line, Tumor
• Chromosome Aberrations
• DNA, Neoplasm (genetics)
• DNA-Binding Proteins (genetics)
• Female
• Gene Dosage
• Genomic Instability (genetics)
• Humans
• Lasers
• Male
• Microdissection (methods)
• Middle Aged
• Nuclear Proteins (genetics)
• Nucleic Acid Hybridization (genetics)
• Oligonucleotide Array Sequence Analysis
• Proto-Oncogene Proteins B-raf (genetics)
• Proto-Oncogene Proteins c-ret (genetics)
• Proto-Oncogene Proteins c-sis (genetics)
• Ribonucleoproteins, Small Nuclear (genetics)
• Thyroid Neoplasms (genetics, pathology)
• Tumor Suppressor Proteins (genetics)
• snRNP Core Proteins