MAPPING OF DNA AMPLIFICATIONS AT 15 CHROMOSOMAL LOCALIZATIONS IN 1875BREAST-TUMORS - DEFINITION OF PHENOTYPIC GROUPS

DNA amplification is frequent in breast cancer and has been associated with specific clinicopathological parameters and/or worsened course o f the disease, In the present work, we were interested iu further defi ning the association linking the occurrence of DNA amplification to th e emergence of specific breast tumor phenotype. To this aim, we studie d by Southern blotting a total of 1875 breast tumor DNAs with 26 probe s mapping at 15 distinct chromosomal localizations, Of the 26 loci tes ted, 11 loci showed elevated levels of amplification, 9 loci showed oc casional and/or low level of DNA copy number increase, and 6 loci show ed very rare or no variation, This allowed us to define six amplified domains mapping at 8p12, 8q24, 11q13, 12q13, 17q12, and 20q13.2, respe ctively, Over 60% of the tumors analyzed presented at least one amplif ication al one of these localizations, Amplifications often covered la rge regions of DNA and bore complex patterns involving coamplification of several colocalized markers, Statistical analysis revealed correla tions associating DNA amplification with breast tumor phenotype, as we ll as sets of preferential coamplifications, Based on these correlatio ns, we defined three subsets of breast cancer according to their patte rns of DNA amplification, The first subset (group A) was organized aro und the amplifications at 11q13 and/or 8p12 and was predominantly comp osed of estrogen receptor-positive tumors and presented a large propor tion of lobular cancers. The second subset (group B) was organized aro und the amplifications of ERBB2 and/or MYC. These tumors were mostly e strogen receptor-negative and of the ductal invasive type, The third s ubset (group C) corresponded to tumors in which no amplification was d etected in tile present screen, Tumors in this group were largely dipl oid and of low histopathological grading.