We have previously documented that transgenic mice expressing SV40 Tag regulated by the rat prostatic steroid-binding protein C3(1) 5'-¯anking region display multistage mammary tumorigenesis. To delineate genetic changes associated with mammary tumor progression, comparative genomic hybridization (CGH) was performed. CGH revealed a consistent gain of the telomeric region of chromosome 6. This region contains the Ki-ras proto-oncogene. Analyses of genomic DNA by Southern blot demonstrated up to 40-fold ampli®cation of the Kiras gene. Ki-ras ampli®cation was detected in 12, 46 and 68% of tumors from 4, 5 and 6 month old mice, respectively, whereas no ampli®cations were found in any preneoplastic mammary tissues. Tumors bearing Ki-ras gene ampli®cation exhibited high levels of Ki-ras RNA and protein. The over-expressed Ki-Ras protein in these tumors appeared functionally active as indicated by the elevated MAP kinase activity. These data demonstrate that while Ki-ras ampli®cation might not be an early event, there is a strong association between Ki-ras ampli®cation and over-expression and mammary tumor progression in this model. This study also shows that CGH is a powerful and useful technique for identifying chromosomal copy number changes during tumor progression, and that this model may provide a predictable in vivo system for studying gene ampli®ca-tion.

Background:Diffuse large B‐cell lymphoma (DLBCL) is the most common subtype of the non‐Hodgkin's lymphoma all over the world and it is extremely heterogeneous both clinically and pathologically. Concurrent MYC and BCL2/BCL6 translocations, the so‐called double hits (DH) has been identified as an important reverse prognostic factor in DLBCL. Chang and his colleagues have published a manuscript to describe the immunophenotypic and genetic characteristics of DLBCL in Taiwan in 2016. In their study, BCL6, rather than BCL2, rearrangement seemed predominant in DH DLBCL although only 3 patients were identified. BCL6‐rearranged DH DLBCL has been less discussed because it accounts for only 20–25% of all cases in the Western countries. Therefore the importance of BCL6 rearrangement in DH DLBCL should be explored in Taiwan.Aims:We would like to confirm the predominance of BCL6 rearrangement in DH DLBCL in Taiwan. In addition, we would like to figure out the phenotypes and the status of Myc and BCL6 protein expression in BCL6‐rearranged DH DLBCL.Methods:We retrieved 154 patients with pathological‐confirmed, newly‐diagnosed DLBCL patients from Shuang‐Ho Hospital, Wan‐Fang Hospital and Taipei Meidcal University Hospital. Fluorescence insitu hybridization (FISH) to detect MYC rearrangement was performed in all patients. BCL2 and BCL6 rearrangements were checked by FISH when positive MYC rearrangement was confirmed. Immunohistochemical (IHC) stains for Myc, BCL2, BCL6, CD10 and MUM1 were done in all patients.Results:Among the 154 patients, 25 of them had MYC translocation (16.2%). Of the 25 MYC‐rearranged patients, concurrent BCL2 or BCL6 translocation was detected in 12 patients. Two‐thirds of them (8 patients) had simultaneous MYC and BCL6 translocations while the other 3 were MYC‐ and BCL2‐rearranged (Figure 1). We had one patient with concurrent MYC, BCL2 and BCL6 translocations, the so‐called triple hits (TH). Taken together, 75% of DH (including TH) DLBCL patients had BCL6 rearrangement and therefore we confirmed the predominance of BCL6 rearrangement in Taiwan. Among DH (including TH) DLBCL patients with BCL6 rearrangement, only 3 out of 9 (33.3%) expressed Myc and BCL6 proteins simultaneously in the IHC stains (Table 1) and consequently, simultaneous overexpression of Myc and BCL6 proteins was not a good surrogate to screen BCL6‐rearranged DH DLBCL. Five patients (55.6%) were non‐germinal center B‐cell (non‐GCB) phenotype in BCL6‐rearranged DH (including TH) patients (Figure 2), indicating the screening of DH with BCL6 rearrangement should include the non‐GCB phenotype of DLBCL.Summary/Conclusion:1. The majority (75%) of DH (including TH) DLBCL in Taiwan had BCL6 rearrangement and it was quite different from data of the Western countries.image2. The concurrent overexpression of Myc and BCL6 proteins in the IHC stains was not a good surrogate to screen BCL6‐rearranged DH DLBCL.3. More than half (55.6%) of BCL6‐rearranged DH (including TH) DLBCL were non‐GCB phenotype, indicating the screening of DH with BCL6 rearrangement should include the non‐GCB phenotype of DLBCL in Taiwan.4. The screening of BCL6‐rearranged DH DLBCL was mandatory in Taiwan.