Accession Number : ADA398340


Title :   Genomic Inprinting of the M6P/IGF2 Receptor: A Novel Breast Cancer Susceptibility Mechanism


Descriptive Note : Final rept. 1 Jul 1998-30 Jun 2001


Corporate Author : DUKE UNIV MEDICAL CENTER DURHAM NC


Personal Author(s) : Jirtle, Randy L.


Full Text : http://www.dtic.mil/get-tr-doc/pdf?AD=ADA398340


Report Date : JUL 2001


Pagination or Media Count : 29


Abstract : Genomic imprinting is an epigenetic phenomenon in mammals that results in the differential expression of the paternally and maternally inherited alleles of a gene. Imprinted genes normally function to control embryonic growth and development. They also are involved in cancer because their functional haploid state makes them vulnerable to being either inactivated or overexpressed. The M6P/IGF2R has been shown to suppress cancer cell growth and is mutated in a number of human cancers, including those that develop in the lung, liver, colon and breast. These findings are consistent with the M6P/IGF2R functioning normally as a tumor suppressor. We have shown that M6P/IGF2R imprinting and receptor IGF2 binding evolved in an ancestor common to marsupials and eutherian mammals. Although M6P/IGF2R is imprinted in lower eutherian mammals, we have demonstrated that it is not imprinted in humans, clarifying previous misconceptions in the literature regarding its imprint status. Our results with breast cancer and Wilms tumor suggest that a mutational event within intron 10 of the M6P/IGF2R, and not disregulation of imprinting, may have resulted in the aberrant monoallelic expression observed in some humans. Therefore, although the M6P/IGF2R normally functions as a tumor suppressor in lung, liver, colon and breast cancer, genomic imprinting at this locus is not involved in the etiology of tumorigenesis.


Descriptors :   *GENES , *BREAST CANCER , ENZYMES , NEOPLASMS , ETIOLOGY , CELLS(BIOLOGY) , SUPPRESSORS , GROWTH(PHYSIOLOGY) , GENOME , ONCOGENESIS.


Subject Categories : BIOCHEMISRTY
      GENETIC ENGINEERING AND MOLECULAR BIOLOGY
      MEDICINE AND MEDICAL RESEARCH


Distribution Statement : APPROVED FOR PUBLIC RELEASE