PMID- 12950019 OWN - NLM STAT- MEDLINE DCOM- 20031024 LR - 20061115 IS - 0022-3417 (Print) IS - 0022-3417 (Linking) VI - 201 IP - 1 DP - 2003 Sep TI - Association of C-MYC amplification with progression from the in situ to the invasive stage in C-MYC-amplified breast carcinomas. PG - 75-82 AB - Human carcinoma in situ of the breast already demonstrates genomic changes found in invasive lesions. However, no specific genetic alterations have previously been identified that are associated with progression from the in situ to the invasive stage. By comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) analysis of an invasive breast carcinoma with a large associated in situ component, high-level amplification of C-MYC was found in the invasive component only. To determine the frequency of this correlation in a panel of 188 invasive breast carcinomas, 18 additional cases with C-MYC amplification were identified. Nine of these cases had a detectable adjacent in situ component. FISH analysis demonstrated increased (>5) C-MYC signals per nucleus in seven invasive components and increased (>4) C-MYC/centromere 8 signal ratios in five of these. None of the associated in situ components demonstrated these increases. The minimal amplified region was defined at 8q24.13-8qter. C-MYC amplification was correlated with overexpression of C-MYC and two of its target genes, TERT and FBL. Thus, C-MYC amplification is the first identified genetic alteration that is associated with progression from the in situ to the invasive stage of breast carcinoma. CI - Copyright 2003 John Wiley & Sons, Ltd. FAU - Robanus-Maandag, Els C AU - Robanus-Maandag EC AD - Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands. FAU - Bosch, Cathy A J AU - Bosch CA FAU - Kristel, Petra M AU - Kristel PM FAU - Hart, Augustinus A M AU - Hart AA FAU - Faneyte, Ian F AU - Faneyte IF FAU - Nederlof, Petra M AU - Nederlof PM FAU - Peterse, Johannes L AU - Peterse JL FAU - van de Vijver, Marc J AU - van de Vijver MJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Pathol JT - The Journal of pathology JID - 0204634 RN - 0 (DNA, Neoplasm) SB - IM MH - Adult MH - Breast Neoplasms/*genetics/pathology MH - Carcinoma in Situ/*genetics/pathology MH - Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology MH - Chromosomes, Human, Pair 8/genetics MH - DNA, Neoplasm/genetics MH - Disease Progression MH - Female MH - Gene Amplification MH - *Genes, myc MH - Humans MH - In Situ Hybridization, Fluorescence MH - Middle Aged MH - Neoplasm Invasiveness MH - Nucleic Acid Hybridization MH - Polymerase Chain Reaction/methods EDAT- 2003/09/02 05:00 MHDA- 2003/10/25 05:00 CRDT- 2003/09/02 05:00 PHST- 2003/09/02 05:00 [pubmed] PHST- 2003/10/25 05:00 [medline] PHST- 2003/09/02 05:00 [entrez] AID - 10.1002/path.1385 [doi] PST - ppublish SO - J Pathol. 2003 Sep;201(1):75-82. doi: 10.1002/path.1385.