A tumor suppressor gene on chromosome 1p32-pter controls the amplification of MYC family genes in breast cancer.
To investigate the possibility of collaboration between telomeric deletion on the short arm of chromosome 1 and genetic amplification similar to that described in human neuroblastoma, 122 human primary breast tumors were examined by restriction fragment length polymorphism analysis for loss of heterozygosity on 1p32-pter and for the three most frequently amplified genetic regions in breast carcinomas (MYC and ERBB2 protooncogenes and the chromosomal region 11q13). Allelic losses at one or more loci on the telomeric part of the short arm of chromosome 1 was observed in 57 (47%) of 122 informative tumors. MYC, ERBB2, and the 11q13 region were amplified in 23, 20, and 21% of breast tumors, respectively. A correlation was found between loss of heterozygosity on chromosome 1p32-pter and amplification of the MYC (formerly c-myc) protooncogene (P = 0.003), suggesting that these two genetic events may collaborate during tumor progression in human breast cancer. These results, together with those obtained in human neuroblastoma, suggest that the distal part of the short arm of chromosome 1 harbors an unidentified tumor suppressor gene(s), whose inactivation may be involved in MYC family gene amplification (an example of genetic instability) in tumors of various cellular origins.
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Laboratoire d'Oncogénétique, Centre René Huguenin, St. Cloud, France.
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Lidereau
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D001943:Breast Neoplasms / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1; D005260:Female; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D016259:Genes, myc / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D012150:Polymorphism, Restriction Fragment Length; D011519:Proto-Oncogenes / Q000235:genetics*
D005819:Genetic Markers