Mechanism of i(6p) formation in retinoblastoma tumor cells

https://doi.org/10.1016/0165-4608(89)90079-4Get rights and content

Abstract

Isochromosome (6p) represents a highly characteristic cytogenetic abnormality of human retinoblastoma (RB) cells and may be important for tumor progression. To elucidate the mechanism by which this abnormal chromosome is formed, 24 RB tumors and three cell lines were studied by means of DNA polymorphisms specific for the short arm and the long arm of chromosome 6. Our results indicate that mitotic nondisjunction leading to trisomy 6 precedes the isochromosome formation. The isochromosome may then be formed by transverse division of the centromere or intrachromosomal chromatid exchange.

References (19)

  • WF Benedict et al.

    Nonrandom chromosomal changes in untreated retinoblastomas

    Cancer Genet Cytogenet

    (1983)
  • A de la Chapelle

    How do human isochromosomes arise?

    Cancer Genet Cytogenet

    (1982)
  • G Balaban et al.

    Abnormalities of chromosome 13 in retinoblastomas from individuals with normal constitutional karyo-types

    Cancer Genet Cytogenet

    (1982)
  • LE Kusnetsova et al.

    Similar chromosomal abnormalities in several retinoblastomas

    Hum Genet

    (1982)
  • J Squire et al.

    Isochromosome 6p, a unique chromosomal abnormality in retinoblastoma: Verification by standard staining techniques, new densitometric methods, and somatic cell hybridisation

    Hum Genet

    (1984)
  • J Squire et al.

    A detailed analysis of chromosomal changes in heritable and nonheritable retinoblastoma

    Hum Genet

    (1985)
  • RS Sparkes et al.

    Regional assignment of esterase D and retinoblastoma to chromosome band 13q14

    Science

    (1980)
  • RS Sparkes et al.

    Gene for hereditary retinoblastoma assigned to human chromosome 13 by linkage to esterase D

    Science

    (1983)
  • G Klein

    The role of gene dosage and genetic transposition in carcinogenesis

    Nature

    (1981)
There are more references available in the full text version of this article.

Cited by (27)

  • Novel 6p rearrangements and recurrent translocation breakpoints in retinoblastoma cell lines identified by spectral karyotyping and mBAND analyses

    2007, Cancer Genetics and Cytogenetics
    Citation Excerpt :

    Increase in the copy number of chromosomal arm 6p is a frequent event in retinoblastoma, and isochromosome 6p is considered to be a hallmark of retinoblastoma [20,23,24]. By examining the relative dosage of polymorphic 6p and 6q alleles in retinoblastoma tumors with i(6p), Horsthemke et al. [25] showed that mitotic nondisjunction leading to trisomy 6p precedes isochromosome 6p formation, as suggested by Squire et al. [20], and that the transverse division of the centromere or intrachromosomal chromatid exchange are the most likely mechanisms behind the subsequent i(6p) formation. Most retinoblastoma tumors with 6p gain are tetrasomic for all 6p genes, but trisomic tumors with no i(6p) were also identified in the study by Squire et al., leading the authors to suggest that an increase in dosage of 6p genes, and not isochromosome formation per se, was the critical event in tumor development [20].

  • Engraftment and growth of patient-derived retinoblastoma tumour in severe combined immunodeficiency mice

    2000, European Journal of Cancer
    Citation Excerpt :

    In another five samples that grew relatively slowly in the mice, two (Rb7p1 and 8p1) had trisomy 1q, one (Rb23p1) had trisomy 1, and one (Rb13p1) had +i(1)(q10) and i(6)(p10). These findings may support the hypothesis that increased gene dosage on 6p and 1q or loss of genes from 6q and 1p may lead to a tumour growth advantage and progression [17–21]. Although the exact nature of genes located at these chromosome sites is not known as yet, some of these regions are non-randomly involved in rearrangements in a variety of tumour types both lympho-haematopoietic and solid tumours indicating that the genes located at these sites may be involved in tumour progression and, therefore, may not be specific to retinoblastoma.

View all citing articles on Scopus

Part of this work was supported by research grants from the Deutsche Forschungsgemeinschaft and Fonds der Chemischen Industrie.

View full text