Loss of alleles at polymorphic loci on chromosome 2 in uveal melanoma

doi:10.1016/0165-4608(86)90136-6

Cancer Genetics and Cytogenetics

Volume 22, Issue 1, May 1986, Pages 45-53

https://doi.org/10.1016/0165-4608(86)90136-6 Get rights and content

Abstract

The loss of alleles at loci on specific chromosomes in some malignant tumors, such as retinoblastoma and Wilms' tumor, suggests that recessive mutations are important in their oncogenesis. We postulate that similar mechanisms may be involved in the formation of uveal melanomas. We studied alleles at autosomal loci in uveal melanoma cells and in the constitutional cells from 19 patients who developed the tumors. We observed loss of alleles only at loci on chromosome #2. This suggests that recessive alleles at some chromosome #2 locus may be important in the oncogenesis of uveal melanomas.

References (61)

G Balaban et al.
Cytogenetics of human malignant melanoma and premalignant lesions
Cancer Genet Cytogenet
(1984)
A Reichmann et al.
Chromosome 6q− in metastatic melanoma involving the large bowel
Cancer Genet Cytogenet
(1984)
JM Trent et al.
Chromsome 6q involvement in human malignant melanoma
Cancer Genet Cytogenet
(1983)
R Becher et al.
Chromosome 6 in malignant melanoma
Cancer Genet Cytogenet
(1983)
D Barker et al.
Restriction sites containing CpG show a higher frequency of polymorphism in human DNA
Cell
(1984)
WK Cavenee et al.
Expression of recessive alleles by chromosomal mechanisms in retinoblastoma
Nature
(1983)
TP Dryja et al.
Homozygosity of chromosome 13 in retinoblastoma
N Engl J Med
(1984)
AL Murphree et al.
Retinoblastoma: Clues to human oncogenesis
Science
(1984)
A Koufos et al.
Loss of alleles on human chromosome 11 during genesis of Wilm's tumour
Nature
(1984)
SH Orkin et al.
Development of homozygosity for chromosome 11p markers in Wilms' tumour
Nature
(1984)

AE Reeve et al.

Loss of Harvey ras allele in sporadic Wilms' tumour

Nature

(1984)

ER Fearon et al.

Somatic deletion and duplication of genes on chromosome 11 in Wilms' tumours

Nature

(1984)

JJ Yunis et al.

Retinoblastoma and subband deletion of chromosome 13

Am J Dis Child

(1978)

RS Sparkes et al.

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

Science

(1982)

E Solomon

Recessive mutation in aetiology of Wilms' tumour

Nature

(1984)

T Maniatis et al.

Molecular Cloning. A Laboratory Manual

LM Kunkel et al.

Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants

J Aldridge et al.

A strategy to reveal high-frequency RFLPs along the human X chromosome

Am J Hum Genet

(1984)

MH Greene et al.

Familial cutaneous malignant melanoma: Autosomal dominant trait possibly linked to the Rh locus

BR Hawkins et al.

Evidence for linkage between HLA and malignant melanoma

Tissue Antigen

(1981)

S Kakati et al.

Chromosomes and causation of human cancer and leukemia. XXII. Karyotypic changes in malignant melanoma

Cancer

(1977)

S Pathak et al.

Involvement of chromosome 6 in rearrangements in human malignant melanoma cell lines

Cytogenet Cell Genet

(1983)

J Cowan et al.

Involvement of 6p in malignant melanoma

Am J Hum Genet

(1984)

M Pedersen et al.

Nonrandom abberations of chromosomes 1, 3, and 9 in human malignant melanoma

Am J Hum Genet

(1984)

XO Breakfield et al.

Structural gene for β-nerve growth factor not defective in familial dysautonomia

U Francke et al.

The human gene for the β subunit of nerve growth factor is located on the proximal short arm of chromosome 1

Science

(1983)

EV Prochownick et al.

Isolation of a cDNA clone for human antithrombin III

J Biol Chem

(1983)

SC Bock et al.

Assignment of the structural gene for the human antithrombin III to chromosome 1q23

Cytogenet Cell Genet

(1984)

J Feder et al.

A DNA polymorphism in close linkage with the proopiomelanocortin gene

Am J Hum Genet

(1983)

J Feder et al.

DNA restriction fragment analysis of the proopiomelanocortin gene in schizophrenia and bipolar disorders

Am J Hum Genet

(1985)

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^☆: Supported by NIH Grants EY07063 and EY05321.

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Loss of alleles at polymorphic loci on chromosome 2 in uveal melanoma☆

Abstract

Cancer Genet Cytogenet

Cancer Genet Cytogenet

Cancer Genet Cytogenet

Cancer Genet Cytogenet

Cell

Expression of recessive alleles by chromosomal mechanisms in retinoblastoma

Nature

Homozygosity of chromosome 13 in retinoblastoma

N Engl J Med

Retinoblastoma: Clues to human oncogenesis

Science

Loss of alleles on human chromosome 11 during genesis of Wilm's tumour

Nature

Development of homozygosity for chromosome 11p markers in Wilms' tumour

Nature

Loss of Harvey ras allele in sporadic Wilms' tumour

Nature

Somatic deletion and duplication of genes on chromosome 11 in Wilms' tumours

Nature

Retinoblastoma and subband deletion of chromosome 13

Am J Dis Child

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

Science

Recessive mutation in aetiology of Wilms' tumour

Nature

Molecular Cloning. A Laboratory Manual

Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants

A strategy to reveal high-frequency RFLPs along the human X chromosome

Am J Hum Genet

Familial cutaneous malignant melanoma: Autosomal dominant trait possibly linked to the Rh locus

Evidence for linkage between HLA and malignant melanoma

Tissue Antigen

Chromosomes and causation of human cancer and leukemia. XXII. Karyotypic changes in malignant melanoma

Cancer

Involvement of chromosome 6 in rearrangements in human malignant melanoma cell lines

Cytogenet Cell Genet

Involvement of 6p in malignant melanoma

Am J Hum Genet

Nonrandom abberations of chromosomes 1, 3, and 9 in human malignant melanoma

Am J Hum Genet

Structural gene for β-nerve growth factor not defective in familial dysautonomia

The human gene for the β subunit of nerve growth factor is located on the proximal short arm of chromosome 1

Science

Isolation of a cDNA clone for human antithrombin III

J Biol Chem

Assignment of the structural gene for the human antithrombin III to chromosome 1q23

Cytogenet Cell Genet

A DNA polymorphism in close linkage with the proopiomelanocortin gene

Am J Hum Genet

DNA restriction fragment analysis of the proopiomelanocortin gene in schizophrenia and bipolar disorders

Am J Hum Genet