NCI CANCERLIT^® Search: Retinoblastoma, Hereditary - September 2001

Last Modified: November 1, 2001

Minimal regions of chromosomal imbalance in retinoblastoma detected by comparative genomic hybridization.
Loss of MHC class II inducibility in hyperplastic tissue in Rb-defective mice.
Quantitation of androgen receptor gene expression in sporadic breast tumors by real-time RT-PCR: evidence that MYC is an AR-regulated gene.

CancerMail from the National Cancer Institute

1
UI - 21411570
AU - Chen D; Gallie BL; Squire JA
TI - Minimal regions of chromosomal imbalance in retinoblastoma detected by comparative genomic hybridization.
SO - Cancer Genet Cytogenet 2001 Aug;129(1):57-63
AD - Division of Cancer Informatics, Ontario Cancer Institute/Princess Margaret Hospital, University Health Network, 610 University Avenue, M5G 2M9, Toronto, Canada.
Mutation of both alleles of the retinoblastoma gene (RB1) initiate oncogenesis in developing human retina, but other common genomic alterations are present in the tumors. In order to sublocalize the altered genomic regions, 50 retinoblastoma tumors were examined by comparative genomic hybridization (CGH). The minimal regions most frequent gained were 1q31 (52%), 6p22 (44%), 2p24-p25 (30%) and 13q32-q34 (12%). The minimal region most frequently lost was 16q22 (14%). The overall total number of gains or losses evident on CGH was significantly greater in those tumors with either or both 6p or 1q gain, than in tumors with neither 6p nor 1q gain suggesting that chromosomal instability may be associated with acquisition of these changes. Genes mapping to 6p22 and 1q31 may be important in tumor development in retina subsequent to the loss of RB1 alleles.

2
UI - 21411587
AU - Eason DD; Coppola D; Livingston S; Shepherd AT; Blanck G
TI - Loss of MHC class II inducibility in hyperplastic tissue in Rb-defective mice.
SO - Cancer Lett 2001 Oct 10;171(2):209-14
AD - Department of Biochemistry and Molecular Biology, University of South Florida, College of Medicine, MDC 7, 12901 Bruce B. Downs Boulevard, Tampa, FL 33612, USA.
Retinoblastoma gene (Rb) defects occur frequently in human tumors. Studies of Rb-defective human tumor cell lines and Rb-/- murine embryonic fibroblasts demonstrate that Rb is required for interferon-gamma (IFN-gamma) induced major histocompatibility complex (MHC) class II expression. MHC class II expressing tumors generate anti-tumor immune responses associated with tumor-specific infiltrating lymphocytes. The role of Rb in IFN-gamma induced MHC class II expression on an endogenous tumor was examined by immunohistochemical staining for IAbeta and Rb on tissues from Rb+/- mice. MHC class II IAbeta is not induced by IFN-gamma in Rb-deficient neoplastic cells, but remains inducible in related normal tissue.

3
UI - 21423239
AU - Bieche I; Parfait B; Tozlu S; Lidereau R; Vidaud M
TI - Quantitation of androgen receptor gene expression in sporadic breast tumors by real-time RT-PCR: evidence that MYC is an AR-regulated gene.
SO - Carcinogenesis 2001 Sep;22(9):1521-6
AD - Laboratoire de Genetique Moleculaire-UPRES JE 2195, Faculte des Sciences Pharmaceutiques et Biologiques, Universite Rene Descartes-Paris V, Paris, France. ivan.bieche@pharmacie.univ-paris5.fr
Little is known of the function and clinical significance of the androgen receptor (AR) in human breast cancer. Paradoxically, synthetic progestins, such as medroxyprogesterone acetate, are used for second line hormone therapy of breast cancer following tamoxifen failure. A sensitive and accurate assay for AR expression in breast tumors is thus required. Here we have developed and validated a real-time RT-PCR assay to quantify AR gene expression at the mRNA level in a series of 131 patients with unilateral invasive primary breast tumors. AR expression varied widely in tumor tissues (by at least 3 orders of magnitude), being underexpressed in 24/131 (18.3%) and overexpressed in 45/131 (34.4%) relative to normal breast tissues. We observed links (or trends) between AR status and age, menopausal status, Scarff-Bloom-Richardson histopathological grade, lymph node status and estrogen receptor alpha and progesterone receptor status. High AR mRNA levels were negatively linked to MYC gene overexpression (P = 8 x 10(-6)), confirming previous in vitro studies. Our results also suggest a role of the ARA70 gene (which encodes a major AR co-activator) in the AR pathway dysregulation observed in breast cancer. This simple, rapid and semi-automated method will be useful for screening cancer patients for altered AR expression and for predicting the response to androgen therapy in AR-related cancer patients.