Supplementary data manuscript II - Conclusion and Perspective

6 Conclusion and Perspective

10.2 Supplementary data manuscript II

Supplementary Figure 1 A model describing the relationship between overall patient survival and tumor DNA indices ranging between 1.11 and 3.0.

Maximally selected log-rank statistic of overall survival in the entire patient cohort excluding patients with tumors having a DNA index ≤1.11. DNA index cut-off point 1.77 separated two neuroblastoma patient groups with significantly different outcomes.

1.0 1.5 2.0 2.5 3.0

12345Standardized log-rank statistic

1.77

DNA index p=0.05

Supplementary Figure 2 Functional dependency between tumor cell DNA index and established clinical and genetic markers. Conditional inference trees showing the functional relationship of DNA index cut-off values and the clinical or genetic markers (A) overall survival (days), (B) INSS stage 4, (C) age at diagnosis >1.5 years and (D) MYCN status.

time (days) time (days) time (days) time (days)

133 Appendix

Supplementary Figure 3 Knockdown efficacy of shRNA targeting p21CIP1 in SH-EP-MYCN neuroblastoma cells. Western Blot showing p21 expression in whole-cell lysates of SH-EP-MYCN cells stably expressing a p21CIP1 shRNA. Cells were additionally treated with tetracycline to repress the MYCN transgene in SH-EP-MYCN cells and/or with doxorubicin to induce DNA damage and p53 activation. The knockdown efficacy is given in percent.

p21CIP1 shRNA scrambled shRNA MYCN

doxo

p21 β-actin T20 T20 T0 T0 T20 T20 T0 T0

+ +

+ -

---

---+

+ +

- ---+

92% 92% 95% 90%

Relative cell number

2N 4N 8N

SH-EP-MYCN-p21on-MYCNoff_untreated

SH-EP-MYCN-p21on-MYCNoff_doxo

SH-EP-MYCN-p21on-MYCNon_untreated

SH-EP-MYCN-p21on-MYCNon_doxo

2N 4N

Relative cell number

33.2±3.7% tetraploid cells 72.6±8.0% tetraploid cells 33.9±3.7% tetraploid cells 78.9±6.4% tetraploid cells

SH-EP-MYCN-p21on-MYCNoff_scramble_untreated

SH-EP-MYCN-p21on-MYCNoff_scramble_doxo

SH-EP-MYCN-p21on-MYCNon_scramble_untreated

SH-EP-MYCN-p21on-MYCNon_scramble_doxo SH-EP-MYCN-p21off-MYCNoff_untreated

SH-EP-MYCN-p21off-MYCNoff_doxo

SH-EP-MYCN-p21off-MYCNon_untreated

SH-EP-MYCN-p21off-MYCNon_doxo

135 Appendix

Supplementary Figure 4 p21CIP1 knockdown induces tetraploidy in p53 wild-type neuroblastoma cells. DNA profiles of untreated or with doxorubicin (doxo) treated (A) SH-EP-MYCN (TET21N) cells stably expressing a shRNA targeting p21CIP1, (B) SH-EP-MYCN (TET21N) stably expressing a scrambled shRNA and (C) SH-EP-MYCN (TET21N) control cells using flow cytometry. MYCN transgene expression was repressed in these cell cultures by addition of tetracycline to the media.

Supplementary Figure 3 MAD2L1 silencing after vincristine induces tetraploidization treatment in near-diploid neuroblastoma cells. Flow cytometric analysis of cell cycle and ploidy in (A) WAC2-shMAD2L1 or WAC2-shSCRAMBLE and (B) SH-EP-shMAD2L1 or SH-EP-shSCRAMBLE (=SCR) cell cultures with/without vincristine (VCR) treatment. Shown are bar-graph quantifications for each cell line and treatment group.

2N G0/1 MAD2L1-on / -VCR MAD2L1-on / +VCR MAD2L1-off / -VCR MAD2L1-off / +VCR

0h 18h 36h 0h 18h 36h 0h 18h 36h 0h 18h 36h MAD2L1 -on / -VCR MAD2L1 -on / +VCR MAD2L1 -off / -VCR MAD2L1-off / +VCR

WAC2-shMAD2L1 SH-EP-shMAD2L1

Patient SexAge (days)Protocol Stage (INSS) Statuscause of deathEvent EFS (days)OS (days)MYCNLOHDNA index_ main cell clonePloidy2n cell clone3rd cell cloneploidy category NB_S_21female909 NB97 1 NED - - 3961 3961 not ampdel/imb1.00 diploid - - UF NB_S_44male1679 NB97 3 STDtumor relapse 522 1655 ampdel/imb1.00 diploid - - UF NB_S_45female539 NB97 1 NED - - 2400 2400 not amp- 1.00 diploid - - UF NB_S_49male7531 NB97 4 STDtherapy in relapseprogress714 875 not amp- 1.00 diploid - - UF NB_S_50male2420 NB97 3 STDtumor progress189 314 not ampdel/imb1.00 diploid - - UF NB_S_52female2207 NB97 3 NED - - 3561 3561 not amp- 1.00 diploid - - UF NB_S_62female419 NB97 3 NED - - 3533 3533 not amp- 1.00 diploid - - UF NB_S_67male1005 NB97 3 R/P- relapse 2276 3619 ampdel/imb1.00 diploid - - UF NB_S_73female437 NB97 2a NED - - 3266 3266 amp- 1.00 diploid - - UF NB_S_74male60 NB97 3 NED - - 3569 3569 not amp- 1.00 diploid - - UF NB_S_78male446 NB97 4 2ndMT- 2nMT 3720 3766 not amp- 1.00 diploid - - UF NB_S_79male505 NB97 4 STDtumor - 195 195 n.d.n.d.1.00 diploid - - UF NB_S_82female3480 NB97 1 NED - - 2189 2189 not ampn.d.1.00 diploid - - UF NB_S_83female1472 NB97 4 NED - - 3422 3422 not ampn.d.1.00 diploid - - UF NB_S_93female3990 NB97 4 STDtumor relapse 764 3555 not amp- 1.00 diploid - - UF NB_S_103male216 NB97 1 NED - - 2184 2184 not ampdel/imb1.00 diploid - - UF NB_S_104male1290 NB97 4 STDtumor relapse 1605 2364 not ampdel/imb1.00 diploid - - UF NB_S_106male4394 NB97 4 STDtumor progress486 1293 not amp- 1.00 diploid - - UF NB_S_110male388 NB97 3 STDtumor progress315 796 amp- 1.00 diploid - - UF NB_S_121female117 NB97 1 NED - - 3409 3409 not ampdel/imb1.00 diploid - - UF NB_S_122male986 NB97 4 STDtumor progress286 373 ampdel/imb1.00 diploid - - UF NB_S_123male1904 NB97 4 STDtumor progress201 207 ampdel/imb1.00 diploid - - UF NB_S_127female906 NB97 4 STDtumor relapse 707 805 ampdel/imb1.00 diploid - - UF NB_S_128male967 NB97 4 STDtumor progress247 344 ampdel/imb1.00 diploid - - UF

Supplementary Table 1 Patient data.

137 Appendix

NB_S_129female472 NB97 2b R/P- progress485 3635 not amp- 1.00 diploid - - UF NB_S_139female1173 NB97 4 NED - - 3395 3395 not amp- 1.00 diploid - - UF NB_S_140female482 NB97 2b STDtherapy- 32 32 ampdel/imb1.00 diploid - - UF NB_S_143male1536 NB97 3 STDtumor progress117 147 ampdel/imb1.00 diploid - - UF NB_S_154female1535 NB97 4 STDtumor relapse 605 708 ampdel/imb1.00 diploid - - UF NB_S_156female625 NB97 4 STDtumor relapse 840 1191 ampdel/imb1.00 diploid - - UF NB_S_159female1239 NB97 4 STDtumor or therapy- 35 35 ampn.d.1.00 diploid - - UF NB_S_163male1652 NB97 3 NED - - 3183 3183 ampdel/imb1.00 diploid - - UF NB_S_164female924 NB97 4 NED - - 3214 3214 not ampn.d.1.00 diploid - - UF NB_S_173male11 NB97 4sR/P- progress1567 3303 not amp- 1.00 diploid - - UF NB_S_174female2831 NB97 3 R/P- relapse 685 2911 not amp- 1.00 diploid - - UF NB_S_177female469 NB97 3 NED - - 3017 3017 not amp- 1.00 diploid - - UF NB_S_178male2925 NB97 4 NED - - 2115 2115 not amp- 1.00 diploid - - UF NB_S_180female156 NB97 2a R/P- progress78 3341 not ampdel/imb1.00 diploid - - UF NB_S_191male1018 NB97 4 STDtumor progress364 1154 ampdel/imb1.00 diploid - - UF NB_S_192female978 NB97 4 STDtumor relapse 1197 1695 ampdel/imb1.00 diploid - - UF NB_S_197female822 NB97 4 STDtumor progress266 283 not ampdel/imb1.00 diploid - - UF NB_S_206female864 NB97 3 R/P- relapse 2062 2616 ampdel/imb1.00 diploid - - UF NB_S_209male1029 NB97 4 NED - - 2818 2818 ampdel/imb1.00 diploid - - UF NB_S_232female1733 NB97 4 NED - - 2344 2344 not amp- 1.00 diploid - - UF NB_S_233male589 NB97 2a NED - - 2401 2401 not ampn.d.1.00 diploid - - UF NB_S_234female727 NB97 3 R/P- progress371 2674 not amp- 1.00 diploid - - UF NB_S_239male1748 NB97 4 STDtumor relapse 510 637 not amp- 1.00 diploid - - UF NB_S_241male2754 NB974 STDtherapyprogress254 256 not amp- 1.00 diploid - - UF NB_S_243male810 NB97 2b STDtumor relapse 916 1376 ampdel/imb1.00 diploid - - UF NB_S_244female1639 NB97 3 R/P- progress200 755 not amp- 1.00 diploid - - UF NB_S_257male942 NB97 4 R/P- relapse 562 2646 not amp- 1.00 diploid - - UF

NB_S_262female1742 NB97 3 NED - - 2541 2541 ampdel/imb1.00 diploid - - UF NB_S_264male4111 NB97 4 NED - - 1459 1459 not amp- 1.00 diploid - - UF NB_S_265female1179 NB97 4 STDtumor relapse 1282 2587 not amp- 1.00 diploid - - UF NB_S_280female16 NB97 4sNED - - 2111 2111 not amp- 1.00 diploid - - UF NB_S_283male10 NB97 4sR/P- progress296 2141 not amp- 1.00 diploid - - UF NB_S_289male3 NB97 3 NED - - 1888 1888 not ampn.d.1.00 diploid - - UF NB_S_295female517 NB97 4 STDtumor relapse 433 711 ampdel/imb1.00 diploid - - UF NB_S_319male13 NB97 1 NED - - 2100 2100 not ampn.d.1.00 diploid - - UF NB_S_320female361 NB97 4 STDtherapy- 211 211 ampdel/imb1.00 diploid - - UF NB_S_325male2219 NB97 4 STDtumor relapse 252 354 ampdel/imb1.00 diploid - - UF NB_S_342male1590 NB04 4 NED - - 1852 1852 not amp- 1.00 diploid - - UF NB_S_343male1157 NB04 3 NED - - 1179 1179 not amp- 1.00 diploid - - UF NB_S_352male92 NB04 4sNED - - 1526 1526 ampdel/imb1.00 diploid - - UF NB_S_362male1676 NB04 2b NED - - 1322 1322 not amp- 1.00 diploid - - UF NB_S_373male85 NB04 4sSTDtumor progress161 209 ampdel/imb1.00 diploid - - UF NB_S_374male2253 NB04 2a STDtumor progress306 752 not ampdel/imb1.00 diploid - - UF NB_S_375male0 NB04 1 NED - - 1240 1240 not amp- 1.00 diploid - - UF NB_S_393female243 NB04 4sNED - - 1118 1118 not amp- 1.00 diploid - - UF NB_S_396female247 NB04 4 NED - - 1290 1290 not amp- 1.00 diploid - - UF NB_S_418male464 NB04 4 STDtumor progress251 347 ampdel/imb1.00 diploid - - UF NB_S_434female134 NB04 4sNED - - 832 832 ampdel/imb1.00 diploid - - UF NB_S_446female633 NB04 4 STDtumor relapse 431 454 ampdel/imb1.00 diploid - - UF NB_S_479female3866 NB04 3 NED - - 654 654 not amp- 1.00 diploid - - UF NB_S_496female1885 NB043 R/P- progress441 700 not amp- 1.00 diploid - - UF NB_S_497male2333 NB04 3 NED - - 656 656 ampdel/imb1.00 diploid - - UF NB_S_506male947 NB04 4 NED - - 321 321 ampdel/imb1.00 diploid - - UF NB_S_515male162 NB04 4 NED - - 396 396 ampdel/imb1.00 diploid - - UF

139 Appendix

NB_S_516male2326 NB04 4 NED - - 551 551 not amp- 1.00 diploid - - UF NB_S_526female2109 NB04 4 NED - - 411 411 not ampdel/imb1.00 diploid - - UF NB_S_534male101 NB04 4sNED - - 488 488 not ampdel/imb1.00 diploid - - UF NB_S_546male907 NB04 4 NED - - 390 390 ampdel/imb1.00 diploid - - UF NB_S_551female700 NB04 4 NED - - 346 346 ampdel/imb1.00 diploid - - UF NB_S_558female953 NB04 4 NED - - 216 216 ampdel/imb1.00 diploid - - UF NB_S_559male989 NB04 4 R/P- relapse 287 305 ampdel/imb1.00 diploid - - UF NB_S_560male2338 NB04 4 NED - - 223 223 ampdel/imb1.00 diploid - - UF NB_S_570male1272 NB04 3 NED - - 185 185 ampdel/imb1.00 diploid - - UF NB_S_571male267 NB04 4 NED - - 142 142 ampdel/imb1.00 diploid - - UF NB_S_398female1099 NB04 2b NED - - 1044 1044 not amp- 1.01 hyperdiploid- - UF NB_S_12male853 NB97 4 NED - - 4132 4132 not ampdel/imb1.02 polyclonal 2.07 - UF NB_S_11male2027 NB97 4 STDtumor relapse 342 457 not amp- 1.02 hyperdiploid- - UF NB_S_590male34 NB04 1 NED - - 23 23 not amp- 1.02 hyperdiploid- - UF NB_S_540male451 NB04 2b NED - - 466 466 not amp- 1.03 hyperdiploid- - UF NB_S_6female144 NB97 4sSTDtumor progress399 419 not amp- 1.04 polyclonal 1.42 - UF NB_S_16female467 NB97 1 NED - - 4240 4240 not amp- 1.04 hyperdiploid- - UF NB_S_293male1602 NB97 4 R/P- relapse 1896 2059 not amp- 1.04 hyperdiploid- - UF NB_S_376female133 NB04 3 STDtumor progress75 125 not amp- 1.04 hyperdiploid- - UF NB_S_533male1215 NB04 4 NED - - 472 472 not ampdel/imb1.04 hyperdiploid- - UF NB_S_200female1188 NB97 4 STDtumor relapse 572 926 not ampn.d.1.05 polyclonal 2.10 - UF NB_S_35male968 NB97 3 R/P- progress1160 3375 not ampdel/imb1.05 hyperdiploid- - UF NB_S_42female552 NB97 4 STDtumor progress334 354 amp- 1.05 hyperdiploid- - UF NB_S_168male330 NB974 NED - - 2457 2457 ampn.d.1.05 hyperdiploid- - UF NB_S_365male291 NB04 4 NED - - 1361 1361 not amp- 1.05 hyperdiploid- - UF NB_S_468male837 NB04 4 R/P- relapse 566 868 ampdel/imb1.05 hyperdiploid- - UF NB_S_462male209 NB04 2a NED - - 690 690 not amp- 1.06 polyclonal 1.30 - UF

NB_S_20female1169 NB97 4 STDtumor relapse 267 666 ampdel/imb1.06 hyperdiploid- - UF NB_S_40female3969 NB97 4 STDtumor progress893 956 ampdel/imb1.06 hyperdiploid- - UF NB_S_454male1691 NB04 4 R/P- progress367 821 not amp- 1.07 polyclonal 1.11 - UF NB_S_326female1964 NB04 4 STDtumor progress441 478 ampdel/imb1.07 polyclonal 1.68 - UF NB_S_214female215 NB97 4 R/P- progress1399 3056 not amp- 1.07 hyperdiploid- - UF NB_S_353female1976 NB04 1 NED - - 1393 1393 not amp- 1.07 hyperdiploid- - UF NB_S_383male504 NB04 4 STDtumor progress349 926 not amp- 1.07 hyperdiploid- - UF NB_S_470male1103 NB04 4 STDtumor progress213 275 not amp- 1.07 hyperdiploid- - UF NB_S_556male1419 NB04 4 NED - - 353 353 not amp- 1.07 hyperdiploid- - UF NB_S_305male1165 NB97 4 STDtumor relapse 711 1128 not amp- 1.08 hyperdiploid- - UF NB_S_455female791 NB04 3 NED - - 865 865 ampdel/imb1.08 hyperdiploid- - UF NB_S_465male1708 NB04 4 R/P- relapse 668 907 not ampdel/imb1.09 polyclonal 1.18 - UF NB_S_34male539 NB97 4 STDtumor relapse 372 378 ampdel/imb1.09 hyperdiploid- - UF NB_S_308male482 NB97 2a NED - - 2099 2099 not ampn.d.1.09 hyperdiploid- - UF NB_S_472female5 NB04 2a NED - - 827 827 not amp- 1.10 polyclonal 1.40 - UF NB_S_439female502 NB04 4 R/P- progress963 1176 not amp- 1.10 polyclonal 2.10 - UF NB_S_4female104 NB97 1 NED - - 2956 2956 not amp- 1.10 hyperdiploid- - UF NB_S_198female2544 NB97 4 STDtumor progress812 1454 not amp- 1.10 hyperdiploid- - UF NB_S_349male1875 NB04 4 STDtherapy in relapserelapse 1002 1381 not ampdel/imb1.10 hyperdiploid- - UF NB_S_432female423 NB04 3 STDtumor relapse 417 526 ampdel/imb1.10 hyperdiploid- - UF NB_S_438male1067 NB04 3 R/P- progress692 1244 not amp- 1.10 hyperdiploid- - UF NB_S_475male207 NB04 4 NED - - 534 534 not amp- 1.10 hyperdiploid- - UF NB_S_562male1812 NB04 4 NED - - 218 218 not ampdel/imb1.10 hyperdiploid- - UF NB_S_355male219 NB044 NED - - 1666 1666 ampdel/imb1.11 polyclonal 2.17 - UF NB_S_278male0 NB97 1 NED - - 2303 2303 not ampn.d.1.11 hyperdiploid- - UF NB_S_370male1537 NB04 4 STDtumor relapse 615 1235 not amp- 1.11 hyperdiploid- - UF NB_S_388male8 NB04 2a NED - - 957 957 not amp- 1.11 hyperdiploid- - UF

141 Appendix

NB_S_395female3488 NB04 1 NED - - 849 849 not amp- 1.11 hyperdiploid- - UF NB_S_425female310 NB04 3 STDtumor progress98 103 ampdel/imb1.11 hyperdiploid- - UF NB_S_543unknown1328 NB04 4 NED - - 335 335 ampdel/imb1.12 polyclonal 1.27 - F NB_S_517male768 NB04 3 NED - - 468 468 not ampdel/imb1.13 hyperdiploid- - F NB_S_545Amale1507 NB04 3 NED - - 393 393 not ampdel/imb1.13 hyperdiploid- - F NB_S_25male127 NB95 4sR/P- relapse 568 2978 not amp- 1.14 polyclonal 1.57 - F NB_S_317female1748 NB90 4 STD2nd MTprogress274 3819 not ampdel/imb1.14 polyclonal 1.68 - F NB_S_41male201 NB97 1 NED - - 3607 3607 not amp- 1.14 hyperdiploid- - F NB_S_92female1424 NB97 4 R/P- relapse 705 3298 not amp- 1.14 hyperdiploid- - F NB_S_213male2146 NB97 4 NED - - 2994 2994 not amp- 1.14 hyperdiploid- - F NB_S_306female94 NB97 4sR/P- progress53 1803 not ampn.d.1.14 hyperdiploid- - F NB_S_536male1383 NB04 4 NED - - 467 467 not amp- 1.14 hyperdiploid- - F NB_S_448female1414 NB04 4 NED - - 692 692 not amp- 1.15 polyclonal 1.69 - F NB_S_421female1057 NB04 3 R/P- relapse 349 1042 not amp- 1.15 hyperdiploid- - F NB_S_488male126 NB04 1 NED - - 339 339 not amp- 1.15 hyperdiploid- - F NB_S_271male35 NB97 1 NED - - 2028 2028 not amp- 1.16 hyperdiploid- - F NB_S_428female1947 NB04 1 NED - - 763 763 not amp- 1.16 hyperdiploid- - F NB_S_463male150 NB04 4sR/P- relapse 655 1524 not ampdel/imb1.16 hyperdiploid- - F NB_S_464male843 NB04 2a STDtherapyprogress225 409 not amp- 1.16 hyperdiploid- - F NB_S_486female1659 NB04 4 NED - - 721 721 not ampn.d.1.16 hyperdiploid- - F NB_S_65male227 NB97 4sR/P- relapse 293 2807 not amp- 1.17 hyperdiploid- - F NB_S_268male49 NB97 1 NED - - 2431 2431 not amp- 1.17 hyperdiploid- - F NB_S_318male1640 NB97 4 NED - - 1846 1846 not ampdel/imb1.17 hyperdiploid- - F NB_S_341female300 NB042a NED - - 1775 1775 not amp- 1.17 hyperdiploid- - F NB_S_578male88 NB04 4sNED - - 47 47 not amp- 1.17 hyperdiploid- - F NB_S_134female2201 NB97 1 NED - - 2985 2985 not ampdel/imb1.18 polyclonal 1.30 - F NB_S_588female166 NB04 4 NED - - 78 78 not amp- 1.18 polyclonal 1.44 - F

NB_S_338female379 NB04 2a R/P- progress10 1772 not amp- 1.18 hyperdiploid- - F NB_S_387male9 NB04 3 NED - - 390 390 not amp- 1.18 hyperdiploid- - F NB_S_417male415 NB04 3 NED - - 1108 1108 not amp- 1.18 hyperdiploid- - F NB_S_350male14 NB04 2a NED - - 1349 1349 not amp- 1.19 hyperdiploid- - F NB_S_369female1651 NB04 4 STDtumor relapse 363 1469 not amp- 1.19 hyperdiploid- - F NB_S_498female112 NB04 2a R/P- progress657 1273 amp- 1.19 hyperdiploid- - F NB_S_528male4 NB04 1 NED - - 463 463 not amp- 1.19 hyperdiploid- - F NB_S_563female70 NB04 2a NED - - 93 93 not amp- 1.19 hyperdiploid- - F NB_S_473male77 NB04 4 NED - - 754 754 not amp- 1.20 polyclonal 1.34 - F NB_S_231male198 NB97 4sSTDtherapy- 53 53 not ampn.d.1.20 polyclonal 2.49 - F NB_S_276male112 NB97 1 R/P- relapse 113 1029 not amp- 1.20 hyperdiploid- - F NB_S_531female849 NB04 4 NED - - 427 427 ampdel/imb1.20 hyperdiploid- - F NB_S_535female0 NB04 2a NED - - 199 199 not amp- 1.20 hyperdiploid- - F NB_S_537male613 NB04 3 NED - - 400 400 not ampdel/imb1.20 hyperdiploid- - F NB_S_572female50 NB04 4sNED - - 91 91 not amp- 1.20 hyperdiploid- - F NB_S_36female907 NB97 4 STDtherapy in relapseprogress491 521 not amp- 1.21 hyperdiploid- - F NB_S_63male130 NB97 4 NED - - 2566 2566 not ampn.d.1.21 hyperdiploid- - F NB_S_263male1308 NB97 3 NED - - 2085 2085 ampdel/imb1.21 hyperdiploid- - F NB_S_404female0 NB04 3 R/P- progress186 797 not amp- 1.21 hyperdiploid- - F NB_S_196male218 NB97 1 NED - - 3013 3013 not amp- 1.22 hyperdiploid- - F NB_S_237female542 NB97 1 NED - - 1946 1946 not ampn.d.1.22 hyperdiploid- - F NB_S_427male204 NB04 2b NED - - 683 683 not amp- 1.22 hyperdiploid- - F NB_S_33female0 NB97 1 NED - - 3965 3965 not amp- 1.23 hyperdiploid- - F NB_S_37male2010 NB974 NED - - 4033 4033 not amp- 1.23 hyperdiploid- - F NB_S_158female638 NB97 2b NED - - 2913 2913 not amp- 1.24 hyperdiploid- - F NB_S_397male1408 NB04 3 STDtumor relapse 540 1120 not amp- 1.24 hyperdiploid- - F NB_S_55male3 NB97 4sNED - - 3451 3451 not amp- 1.25 hyperdiploid- - F

143 Appendix

NB_S_64male115 NB97 1 NED - - 3524 3524 not amp- 1.25 hyperdiploid- - F NB_S_494male441 NB04 4 NED - - 668 668 ampdel/imb1.25 hyperdiploid- - F NB_S_337female64 NB04 3 NED - - 1491 1491 not amp- 1.26 hyperdiploid- - F NB_S_507male1360 NB04 4 NED - - 608 608 not amp- 1.26 hyperdiploid- - F NB_S_9male4410 NB97 4 STDtumor progress157 1429 not amp- 1.27 polyclonal 1.32 - F NB_S_430male75 NB04 4sNED - - 712 712 not amp- 1.27 hyperdiploid- - F NB_S_592male10 NB04 2a NED - - 16 16 not amp- 1.27 hyperdiploid- - F NB_S_525female264 NB04 4sNED - - 495 495 not amp- 1.28 polyclonal 1.82 - F NB_S_194female80 NB97 4sNED - - 2883 2883 not ampdel/imb1.28 hyperdiploid- - F NB_S_245male3175 NB97 4 R/P- relapse 1318 3181 not ampn.d.1.28 hyperdiploid- - F NB_S_384female118 NB04 1 NED - - 910 910 not amp- 1.28 hyperdiploid- - F NB_S_410male2 NB04 2a NED - - 1210 1210 not amp- 1.28 hyperdiploid- - F NB_S_544female216 NB04 1 NED - - 106 106 not ampdel/imb1.28 hyperdiploid- - F NB_S_574male0 NB04 2a R/P- progress125 255 not amp- 1.28 hyperdiploid- - F NB_S_474female5578 NB04 3 NED - - 363 363 not ampdel/imb1.29 polyclonal 1.15 - F NB_S_469female12 NB04 2a NED - - 623 623 not amp- 1.29 polyclonal 1.40 - F NB_S_467male39 NB04 1 NED - - 562 562 not amp- 1.30 polyclonal 1.40 - F NB_S_38female445 NB97 4 NED - - 3866 3866 not ampdel/imb1.30 hyperdiploid- - F NB_S_60male357 NB97 3 NED - - 3353 3353 not ampn.d.1.30 hyperdiploid- - F NB_S_75male79 NB97 4sNED - - 3243 3243 not amp- 1.30 hyperdiploid- - F NB_S_95male333 NB95 3 R/P- progress1676 5170 not amp- 1.30 hyperdiploid- - F NB_S114male460 NB97 1 NED - - 3080 3080 not amp- 1.30 hyperdiploid- - F NB_S_513female38 NB04 2a NED - - 599 599 not amp- 1.30 hyperdiploid- - F NB_S_557female564 NB041 NED - - 246 246 not amp- 1.30 hyperdiploid- - F NB_S_422female121 NB04 3 R/P- progress74 823 not amp- 1.31 polyclonal 1.35 - F NB_S_302male0 NB97 1 NED - - 1995 1995 not amp- 1.31 polyclonal 1.46 - F NB_S_161male85 NB97 4sNED - - 2706 2706 not ampn.d.1.31 hyperdiploid- - F

145 Appendix

NB_S_267female410 NB97 1 NED - - 2338 2338 not amp- 1.31 hyperdiploid- - F NB_S_450female437 NB04 1 NED - - 561 561 not amp- 1.31 hypodiploid- - F NB_S_501male4102 NB04 1 NED - - 475 475 not amp- 1.31 hyperdiploid- - F NB_S_423male363 NB04 2a NED - - 975 975 not ampdel/imb1.32 polyclonal 2.30 - F NB_S_476female1604 NB04 4 NED - - 697 697 not ampdel/imb1.32 hyperdiploid- - F NB_S_252female26 NB97 2b NED - - 2523 2523 not amp- 1.33 hyperdiploid- - F NB_S_385female1 NB04 3 R/P- progress150 1032 not amp- 1.33 hyperdiploid- - F NB_S_458female245 NB04 1 NED - - 850 850 not amp- 1.33 hyperdiploid- - F NB_S_460male1852 NB04 1 NED - - 674 674 not amp- 1.33 hyperdiploid- - F NB_S_8female494 NB97 1 NED - - 4052 4052 not amp- 1.34 polyclonal 1.40 - F NB_S_408female28 NB04 3 R/P- progress188 1330 not amp- 1.34 polyclonal 2.67 - F NB_S_144female77 NB97 4sR/P- progress1006 4566 not amp- 1.34 hyperdiploid- - F NB_S_296male13 NB97 3 NED - - 2186 2186 not amp- 1.34 hyperdiploid- - F NB_S_402male279 NB04 3 R/P- progress738 1144 not amp- 1.34 hyperdiploid- - F NB_S_521female634 NB04 3 NED - - 430 430 not amp- 1.34 hyperdiploid- - F NB_S_298female128 NB97 4sNED - - 2042 2042 not amp- 1.35 polyclonal 1.06 1.44 F NB_S_24female223 NB97 3 NED - - 4062 4062 not ampdel/imb1.35 hyperdiploid- - F NB_S_193male7852 NB97 4 R/P- progress1361 2188 not amp- 1.35 hyperdiploid- - F NB_S_379male258 NB04 4sNED - - 952 952 not amp- 1.35 hyperdiploid- - F NB_S_28female440 NB97 1 NED - - 3753 3753 not amp- 1.36 hyperdiploid- - F NB_S113female4669 NB97 1 NED - - 2083 2083 not ampn.d.1.36 hyperdiploid- - F NB_S_137male203 NB97 4 NED - - 3166 3166 not amp- 1.36 hyperdiploid- - F NB_S_172female58 NB97 4sNED - - 2609 2609 not amp- 1.36 hyperdiploid- - F NB_S_361male305 NB044sR/P- progress301 1133 not amp- 1.36 hyperdiploid- - F NB_S_366female66 NB04 4sNED - - 1452 1452 not amp- 1.36 hyperdiploid- - F NB_S_591female0 NB04 1 NED - - 126 126 not amp- 1.37 polyclonal 1.20 1.60 F NB_S_359female528 NB04 4 NED - - 1473 1473 not ampn.d.1.37 hyperdiploid1.43 1.65 F

NB_S_415female297 NB04 4sNED - - 892 892 not amp- 1.37 polyclonal 2.20 - F NB_S_183male4545 NB90 3 STDtumor relapse 1490 3865 not ampdel/imb1.37 hyperdiploid- - F NB_S_248male789 NB97 4 NED - - 2251 2251 amp- 1.37 hyperdiploid- - F NB_S_294male698 NB97 3 NED - - 1587 1587 not amp- 1.37 hyperdiploid- - F NB_S_406male165 NB04 4sNED - - 814 814 not amp- 1.37 hyperdiploid- - F NB_S_445male1865 NB04 4 NED - - 912 912 not amp- 1.37 hyperdiploid- - F NB_S_547female762 NB04 1 NED - - 311 311 not amp- 1.37 hyperdiploid- - F NB_S_594female9 NB04 3 NED - - 43 43 not amp- 1.37 hyperdiploid- - F NB_S_490female343 NB04 4 NED - - 348 348 not amp- 1.38 polyclonal 1.20 - F NB_S_585male473 NB04 3 NED - - 62 62 not amp- 1.38 polyclonal 1.60 - F NB_S102male148 NB97 4sNED - - 3599 3599 not amp- 1.38 hyperdiploid- - F NB_S119female426 NB97 3 NED - - 3405 3405 not amp- 1.38 hyperdiploid- - F NB_S_216male47 NB97 3 R/P- progress1128 2793 not amp- 1.38 hyperdiploid- - F NB_S_255male228 NB97 2b NED - - 2389 2389 not amp- 1.38 hyperdiploid- - F NB_S_145female480 NB97 2a NED - - 3285 3285 not amp- 1.39 hyperdiploid- - F NB_S_347female700 NB04 1 NED - - 1307 1307 not amp- 1.39 hyperdiploid- - F NB_S_32female743 NB97 1 NED - - 3301 3301 not amp- 1.40 hyperdiploid- - F NB_S_212female453 NB97 2a R/P- progress651 2773 not amp- 1.40 hyperdiploid- - F NB_S_297female93 NB97 4sNED - - 2002 2002 not amp- 1.40 hyperdiploid- - F NB_S_552male61 NB04 1 NED - - 57 57 not amp- 1.40 hyperdiploid- - F NB_S_580female154 NB04 2b NED - - 67 67 not amp- 1.40 hyperdiploid- - F NB_S_582male5 NB04 1 NED - - 37 37 not amp- 1.41 polyclonal 2.80 - F NB_S_301female528 NB97 1 NED - - 1907 1907 not amp- 1.41 hyperdiploid- - F NB_S_357male116 NB044sNED - - 1184 1184 not ampn.d.1.41 hyperdiploid- - F NB_S_368male75 NB04 1 NED - - 1586 1586 not amp- 1.41 hyperdiploid- - F NB_S_550female128 NB04 4sNED - - 253 253 not amp- 1.41 hyperdiploid- - F NB_S_207female344 NB97 3 NED - - 3055 3055 not amp- 1.42 hyperdiploid- - F

147 Appendix

NB_S_270male220 NB97 1 NED - - 2210 2210 not ampn.d.1.42 hyperdiploid- - F NB_S_303male75 NB97 4sSTDtumor - 85 85 ampdel/imb1.42 hyperdiploid- - F NB_S_327female0 NB97 2a R/P- progress70 1594 not amp- 1.42 hyperdiploid- - F NB_S_363male42 NB04 2a R/P- progress83 1279 not amp- 1.42 hyperdiploid- - F NB_S_508male0 NB04 2b R/P- progress68 1218 not amp- 1.42 hyperdiploid- - F NB_S_514female745 NB04 4 NED - - 569 569 not ampdel/imb1.42 hyperdiploid- - F NB_S_548male220 NB04 4sNED - - 386 386 not amp- 1.42 hyperdiploid- - F NB_S_424male448 NB04 3 R/P- progress295 897 not amp- 1.43 polyclonal 1.49 - F NB_S_51male37 NB97 1 NED - - 3669 3669 not amp- 1.43 hyperdiploid- - F NB_S_367male1513 NB04 2a NED - - 1082 1082 not amp- 1.43 hyperdiploid- - F NB_S_449female751 NB04 1 NED - - 393 393 not amp- 1.44 polyclonal 1.10 - F NB_S_182female385 NB97 1 R/P- relapse 107 3283 not amp- 1.44 hyperdiploid- - F NB_S_260male1310 NB97 1 NED - - 2689 2689 not ampn.d.1.44 hyperdiploid- - F NB_S_518female212 NB04 4 NED - - 275 275 not ampdel/imb1.44 hyperdiploid- - F NB_S_26female1017 NB97 4 R/P- relapse 921 4163 not ampdel/imb1.45 triploid- - F NB_S115male121 NB97 4 STDtumor relapse 326 391 ampdel/imb1.45 triploid- - F NB_S_146female1215 NB97 2b NED - - 2689 2689 not amp- 1.45 triploid- - F NB_S_210female308 NB97 4sNED - - 2784 2784 not amp- 1.45 triploid- - F NB_S_381female581 NB04 2a R/P- progress172 1519 not amp- 1.45 triploid- - F NB_S_478female136 NB04 2a R/P- progress53 555 not amp- 1.45 triploid- - F NB_S_76male1391 NB97 1 NED - - 3349 3349 not amp- 1.46 triploid- - F NB_S_94female245 NB97 1 NED - - 2933 2933 not amp- 1.46 triploid- - F NB_S_254male4 NB97 1 NED - - 2508 2508 not amp- 1.46 triploid- - F NB_S_419male91 NB041 NED - - 663 663 not amp- 1.46 triploid- - F NB_S_523male73 NB04 1 NED - - 279 279 not ampdel/imb1.46 triploid- - F NB_S_527male50 NB04 4sNED - - 397 397 not amp- 1.47 polyclonal 1.60 - F NB_S_39female512 NB97 1 NED - - 3831 3831 not ampdel/imb1.47 triploid- - F

NB_S109female374 NB97 2a R/P- progress134 3385 not amp- 1.47 triploid- - F NB_S_135male123 NB97 1 NED - - 3149 3149 not amp- 1.47 triploid- - F NB_S_286female8983 NB97 4 STDtumor progress645 899 not amp- 1.47 triploid- - F NB_S_380male53 NB04 1 NED - - 1186 1186 not amp- 1.47 triploid- - F NB_S_500female1533 NB04 1 NED - - 351 351 not amp- 1.47 triploid- - F NB_S_542male323 NB04 3 NED - - 358 358 not amp- 1.47 triploid- - F NB_S_17male417 NB97 2b NED - - 3707 3707 not amp- 1.48 triploid- - F NB_S118female21 NB97 2b NED - - 3273 3273 not ampdel/imb1.48 triploid- - F NB_S_132male10 NB97 1 NED - - 2055 2055 not amp- 1.48 triploid- - F NB_S_167male506 NB97 4 NED - - 2798 2798 not amp- 1.48 triploid- - F NB_S_259female1265 NB97 2a NED - - 818 818 not ampn.d.1.48 triploid- - F NB_S_444male636 NB04 2a NED - - 952 952 not amp- 1.48 triploid- - F NB_S_509female534 NB04 3 NED - - 532 532 not amp- 1.48 triploid- - F NB_S_482female1733 NB97 4 STDtherapy in relapserelapse 635 682 not amp- 1.49 polyclonal 1.43 - F NB_S112female666 NB97 2a STDtumor progress56 522 not ampdel/imb1.49 triploid- - F NB_S_141male465 NB97 1 NED - - 2673 2673 not amp- 1.49 triploid- - F NB_S_312female40 NB97 1 NED - - 1526 1526 not amp- 1.49 triploid- - F NB_S_332male134 NB04 4sNED - - 1834 1834 not amp- 1.49 triploid- - F NB_S_399male129 NB04 2b NED - - 1082 1082 not amp- 1.49 triploid- - F NB_S_597female335 NB04 3 NED - - 21 21 not amp- 1.49 triploid- - F NB_S_453female679 NB04 1 NED - - 731 731 not amp- 1.50 polyclonal 1.16 - F NB_S_586female619 NB04 3 NED - - 66 66 not ampdel/imb1.50 polyclonal 1.34 - F NB_S_581female871 NB04 1 NED - - 20 20 not amp- 1.50 polyclonal 1.39 - F NB_S_492male417 NB042a NED - - 573 573 not ampdel/imb1.50 polyclonal 1.60 - F NB_S_324female83 NB04 1 NED - - 15 15 not amp- 1.50 polyclonal 1.67 - F NB_S_133male497 NB97 1 NED - - 3132 3132 not amp- 1.50 triploid- - F NB_S_229female2008 NB97 1 NED - - 2468 2468 not ampn.d.1.50 triploid- - F

Im Dokument MYCN-dependent and -independent mechanisms targeting drug-induced DNA damage response and chromosomal instability in neuroblastoma cells (Seite 131-186)