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  • Fer 1 br Fig Amplifications of FGFR

    2020-08-12

    37
    Fig. 1 Amplifications of FGFR1 (Cases 30, 8, and 9) (A-H), ZNF703 (Case 18) (I), and MYC (Cases 19 and 53) (J-L) (orange, gene-specific signals; green, signals for the centromeric regions on which the specific genes are located). In Panel D, paired signals of FGFR1 and centromere 8 (small arrows) and large signals of centromere 8 surrounded by numerous FGFR1 (large arrows) signals were observed (D, triple-band filter; E, SpectrumGreen™-spe-cific filter; F, SpectrumOrange™-specific filter). Panels K and L showed co-amplification of MYC and centromere 8. PC: PC-subtype. Scale bar: 10 μm.
    Amplicons in breast cancers 39
    Fig. 3 Amplicon on 11q13. Overlapped loose clusters of CCND1 (orange) and small signals of centromere 11 (green) were found in the imprinted Fer 1 (A, triple-band filter; B, SpectrumGreen™-specific filter; Case 69). Dual-color FISH on FFPE tissue shows co-localization of CCND1 (green signals) and C11ORF30 (orange signals) (C, Case 4). Scale bar: 10 μm.
    in Fig. 3A and B. Among tumors that yielded amplification of CCND1, 19 of 40 (48%) exhibited co-amplification of C11ORF30 (Fig. 3C). Conversely, no amplification of C11ORF30 was observed without co-amplification of CCND1.
    The HSR-type amplification of ERBB2 was found in 31 tu-mors (Fig. 2C). In eight of these 31, the clustered ERBB2 sig-nals were found near CEP17 signals (PC subtype); in the other
    Fig. 4 Amplicon on 17q. CoPoly-type, PC-subtype amplification of ERBB2 (orange) and centromere 17 (green) on imprinted cells (A, Case 103; B, Case 29). Numerous minute paired signals were found in (A); small ERBB2 signals aggregated around the large centromeric signals were found in (B). Normal lymphocytes with two paired signals are seen at the corners. Note the co-amplification of CPD (orange) and ERBB2 (green) in Case 83 (C), and of BIR5 (orange) and ERBB2 (green) in Case 14 (D, triple-band filter: E, SpectrumGreen™-specific filter). Scale bar: 10 μm.
    Table 2 Co-amplification of non-syntenic genes
    Case No.
    H L
    H H H
    H M
    H
    H H
    H H H
    M
    H L
    H H H H H H L H
    H
    L H M
    H
    C
    H
    D C
    D C X L
    C H
    H H D H H H H H L
    H H H H
    H
    D H
    H
    H
    H H
    H D
    H
    H H H
    C H D
    H
    H H
    H
    H H
    H H H
    C H D
    H C
    H H H H H H C
    H
    L
    C H L
    H
    H H C
    L
    H L
    H
    L
    C
    H
    H H
    H
    H
    C
    C
    C H
    C
    L
    Note. Bold, amplification in non-PC subtype; normal, amplification in PC subtype.
    Abbreviations: H, HSR-type amplification; L, Low-level amplification; M, Monosomy-type amplification; D, DM-type amplification; C, Co-amplified/polysomy-type amplification; X, Mixed HSR- and DM-type amplification.
    Amplicons in breast cancers 41
    Fig. 5 Amplicons containing non-syntenic genes. Dual-color FISH on imprinted cells shows superimposed signals for FGFR1 (orange) and CCND1 (green) in Case 3 (A, triple-band filter; B, SpectrumGreen™-specific filter). In Case 7 (C), co-amplification of ZNF703 (orange) and CCND1 (green) was observed in single nuclei but in different amplicons. Panel D shows a schematic diagram of the amplification status of Case 3. Clustered signals for FGFR1 (orange) and ERBB2 (green) were found separated in Case 13 (E), but in close association in Case 14 (F, triple-band filter; G, SpectrumGreen™-specific filter). Panel H shows a schematic diagram of the amplification status of Case 14. Scale bar: 10 μm.
    23 tumors, the clustered ERBB2 signals were not localized with the CEP17 signals, suggesting that these amplicons were located ectopically. The CoPoly type was found in seven tu-mors where mean (per cell) signals for both ERBB2 and CEP17 exceeded 10. In two of these seven specimens, the am-plified signals of ERBB2 and CEP17 were separated (Cases 18 and 89). In the other five of these seven specimens, paired sig-nals for ERBB2 and CEP17 were found scattered (Fig. 4A) or clustered (Fig. 4B), in different nuclei or in single nuclei. In 
    Case 29, a strong centromere-17 signal was surrounded by nu-merous ERBB2 signals, as shown in Fig. 4B.
    The amplified genes flanking ERBB2, such as MED1, CDC6, and TOP2A, were frequently co-localized with ampli-fied ERBB2; the frequency of amplification gradually de-creased with distance from ERBB2 (Fig. 2C). ERBB2 and the genes more remote from ERBB2 on 17p (such as CPD, PPM1D, and BIRC5) were occasionally co-amplified in the same amplicon, as shown in Fig. 4C-E. Case 7 presented a