Multicolor Spectral Karyotyping of Human Chromosomes

Schröck, Evelin; Manoir, Stanislas du; Veldman, Timothy; Schoell, Brigitte; Wienberg, Johannes; Ferguson-Smith, Malcolm A.; Ning, Yi; Ledbetter, David H.; Bar‐Am, Irit; Soenksen, Dirk; Garini, Yuval; Ried, Thomas

doi:10.1126/science.273.5274.494

Cited by 1,596 publications

(947 citation statements)

References 7 publications

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“…The chromosome spreads were subjected to spectral karyotyping (SKY), a recently developed molecular cytogenetic technique in which each chromosome is painted a di erent color by hybridization to¯uorescent probes (Schrck et al, 1996). SKY allows an unambiguous identi®cation of each chromosome, an extremely di cult task in early embryos by G-or DAPIbanding.…”

Section: Brca1 117/7 Embryos Show Chromosomal Instabilitymentioning

confidence: 99%

A targeted disruption of the murine Brca1 gene causes γ-irradiation hypersensitivity and genetic instability

et al. 1998

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Germline mutations of the Brca1 gene are responsible for most cases of familial breast and ovarian cancers, but somatic mutations are rarely detected in sporadic events. Moreover, mouse embryos de®cient for Brca1 have been shown to die during early embryogenesis due to a proliferation defect. These ®ndings seem incompatible with the tumor suppress function assigned to this gene and raise questions about the mechanism by which Brca1 mutations cause tumorigenesis. We now directly demonstrate that BRCA1 is responsible for the integrity of the genome. Murine embryos carrying a Brca1 null mutation are developmentally retarded and hypersensitive to girradiation, suggesting a failure in DNA damage repair. This notion is supported by spectral karyotyping (SKY) of metaphase chromosomes, which display numerical and structural aberrations. However, massive chromosomal abnormalities are only observed when a p53 7/7 background is introduced. Thus, a p53 dependent cell cycle checkpoint arrests the mutant embryos and prevents the accumulation of damaged DNA. Brca1 7/7 ®broblasts are not viable, nor are Brca1 7/7 : p53 7/7 ®broblasts. However, proliferative foci arise from Brca1 7/7 : p53 7/7 cells, probably due to additional mutations that are a consequence of the accumulating DNA damage. We believe that the increased incidence of such additional mutations accounts for the mechanism of tumorigenesis associated with Brca1 mutations in humans.

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Section: Brca1 117/7 Embryos Show Chromosomal Instabilitymentioning

confidence: 99%

A targeted disruption of the murine Brca1 gene causes γ-irradiation hypersensitivity and genetic instability

et al. 1998

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show abstract

“…Subsequently, spreads were hybridized with a probe mixture supplied by Applied Spectral Imaging (ASI, Carlsbad, Calif.). The probe mixture contained 24 whole chromosome painting probes, labeled with combinations of five different fluorescent dyes (Spectrum Green, Spectrum Orange, Texas Red, Cyanine [Cy] 5 and Cy5.5) [16]. The probe (SKY™ mixture) was denatured at 75°C for 7 min and incubated at 37°C for 1 hr.…”

Section: Spectral Karyotypingmentioning

confidence: 99%

Clonal chromosomal aberrations in simian virus 40‐transfected human thyroid cells and in derived tumors developed after in vitro irradiation

Zitzelsberger

Bruch²,

Smida³

et al. 2001

Intl Journal of Cancer

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“…This technique, along with the technically similar spectral karyotyping (SKY), has greatly facilitated the identification of chromosome material involved in chromosomal rearrangements even in sup-optimal chromosome preparations. 12 Used in combination, the 2 techniques allow chromosomal alterations in human tumours to be characterised more extensively than was previously possible by G-banding alone. A genome wide search for chromosomal abnormalities in SCLC will identify regions of deletion and gain likely to contain genes involved in the development of this disease.…”

mentioning

confidence: 99%

Chromosomal alterations in small cell lung cancer revealed by multicolour fluorescence in situ hybridization

Ashman

Brigham

Cowen

et al. 2002

Intl Journal of Cancer

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Small cell lung cancer (SCLC) is a major cause of cancer related morbidity and mortality. Karyotypic studies have revealed numerous chromosomal aberrations in most SCLC however, classical G-banding analysis is unable to fully characterise complex marker chromosomes. Recent developments in molecular cytogenetics now allow accurate identification of the chromosomal components of complicated rearrangements. We have applied the technique of multicolour fluorescence in situ hybridization (M-FISH) in combination with comparative genomic hybridization (CGH) to the analysis of 5 SCLC cell lines and 1 primary tumour specimen to characterise the chromosomal abnormalities. CGH analysis identified many similarities between specimens, with frequent DNA copy number decreases on chromosomes 3p, 5q, 10, 16q, 17p and frequent gains on 3q, 1p, 1q and 14q. In contrast, M-FISH analysis revealed a large number of structural abnormalities, with each specimen demonstrating an individual pattern of chromosomal translocations. Forty different translocations were identified with the vast majority (39) being unbalanced. Chromosome 5 was the most frequently rearranged chromosome (9 translocations) followed by chromosomes 2, 10 and 16 (6 translocations each). Further investigation of these frequently involved chromosomes is warranted to establish whether consistent break points are involved in these translocations, causing dysregulation of specific genes that are crucial for tumour progression and secondly to identify the affected genes.

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Multicolor Spectral Karyotyping of Human Chromosomes

Cited by 1,596 publications

References 7 publications

A targeted disruption of the murine Brca1 gene causes γ-irradiation hypersensitivity and genetic instability

A targeted disruption of the murine Brca1 gene causes γ-irradiation hypersensitivity and genetic instability

Clonal chromosomal aberrations in simian virus 40‐transfected human thyroid cells and in derived tumors developed after in vitro irradiation

Chromosomal alterations in small cell lung cancer revealed by multicolour fluorescence in situ hybridization

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