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(1)VU Research Portal. Breaking the Cancer Genome Code for Patient Care Sie, D.L.S.. 2017. document version Publisher's PDF, also known as Version of record. Link to publication in VU Research Portal. citation for published version (APA) Sie, D. L. S. (2017). Breaking the Cancer Genome Code for Patient Care.. General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ? Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. E-mail address: vuresearchportal.ub@vu.nl. Download date: 14. Oct. 2021.

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(104) 0 26 0 17 0 0 34 5 77 63 0 0 1 2725 4294 7217 12 1052 438 (41.6%) 841 (79.9%) 2574 3 (0.1%) 10 (0.39%). 100.0% 0.0% 16.5%. 100%. 8.1% — — 44.3% —. 590 11/0/6.17 0.79/0.35/1.62 3208 2.09. 6.1% — — 54.3% —. 4.3% 3.3% 0.1% 0.2% 0.2% 0.0%. 309 242 9 16 13 1. 4.0% 2.4% 0.3% 0.5% 0.8% 0.5%. 50.1%. 3626. 35.5%. 14.5%. 99.7% 0.2%. 0% 0.4% 0% 0.2% 0% 0% 0.5% 0.1% 1.1% 0.9% 0% 0% 0% 37.6% 59.3%. 66.0%. 49.5%. 7242. 0.3% 0.8% 0% 0% 0% 0% 0.5% 0% 0.5% 0.3% 0% 0% 0% 33.5% 64.1%. 12.3/5.1/6.17 0.71/0.41/1.58 2187 1.94. 327. 248 79 8 10 7 8. 5544. 2395 1730 (72.2%) 2294 (95.8%) 3,149 4 (0.1%) 16 (0.51%). 1900 5195. 1464 6069 12 65 50 61 22 29 3 14 25 224 5 145 1. 8189. 12,979. 10,000 100%. ClinVar variants. dbSNP variants. — — 26.7% —. 4.0%. 3.0% 1.0% 0.1% 0.1% 0.1% 0.1%. 67.7%. 38.5%. 29.2%. 23.2% 63.4%. 17.9% 74.1% 0.1% 0.8% 0.6% 0.7% 0.3% 0.4% 0.0% 0.2% 0.3% 2.7% 0.1% 1.8% 0.0%. 100%. — — >0.999999 —. 0.5242. 0.6467 0.6380 0.6179 0.8644 0.9377 0.0269. 0.0027. 0.9950 0.9674 0.0012 0.0001 0.4966 0.2770. >0.999999 >0.999999. >0.999999 >0.999999 0.5727 0.9526 0.8757 0.9090 0.7108 0.8027 0.5184 0.2628 0.7318 0.9987 0.4597 >0.999999 >0.999999. Somatic mutations like dbSNP (P = 1) or ClinVar (P = 0). Probabilitya. Characteristics for somatic mutations, dbSNP, and ClinVar variants. (UTR) Untranslated region; (GERP) Genomic Evolutionary Rate Profiling (negative scores: evolutionary unconstrained genomic positions; high scores: constrained positions); (BU ORChID) OH Radical Cleavage Intensity Database (low scores: resistant to attack by the hydroxyl radical; high scores: sensitive); (LADs) lamina-associated domains; (Ti/Tv) transition/ transversion ratio. a The probability that the somatic mutations are distributed closer to the dbSNP variants (probability = 1) than to the ClinVar variants (probability = 0) is given for each feature. Probability values in bold print are significant after Bonferroni correction for multiple testing. b Genomic regions were filtered for unique 50-mer mapability and genomic read coverage $20. c PolyPhen algorithm predicts that a mutation is benign, possibly damaging, or probably damaging according to probability intervals [0, 0.2], [0.2, 0.85], and [0.85, 1], respectively. d A methylation percentage of $50% was regarded as ‘‘methylated.’’ e The genomic coverage of LADs is 41.8%.. 6.94/0.13/5.64 0.63/0.58/1.52 204 2.27. 23. Total (unique). Other characteristics GERP scores (min, median, max) BU ORChID scores (min, median, max) Lamin B1 associated domains (LADs)e Ti/Tv. 15 9 1 2 3 2. 248. 62 28 (45.2%) 61 (98.4%) 186 0 (0%) 3 (1.6%). 376 0. 1 3 0 0 0 0 2 0 2 1 0 0 0 126 241. 376. NonB DNA (>1 nonB sequence per site possible) Inverted repeat Short tandem repeat G quadruplex motif Z DNA motif Direct repeat Mirror repeat. Total. Filtered variantsb Mutation effect (PolyPhen and SIFT) Nonsense Missense Stop-lost Coding-synonymous Splice-3 Splice-5 UTR-3 UTR-5 Near-gene-3 Near-gene-5 Stop-gained-near-splice Missense-near-splice Coding-synonymous-near-splice Intron Intergenic PolyPhen score,c predicted effect of mutation Unknown >0.85 (probably damaging) Mutations at cytosine residuesd At CpG sites (1.4% genomic coverage) Methylated $50% in GM12878 lymphoblast Methylated $50% in H1 hESC stem cell At nonCpG sites (37.3% genomic coverage) Methylated $50% in GM12878 lymphoblast Methylated $50% in H1 hESC stem cell. 382. Somatic mutations. Features of somatic mutations compared to SNPs and disease-associated mutations. TOTAL VARIANTS. Table 2.. &;9-@5/9A@-@5;:?2;A:05:@4141-8@4E.8;;0/;9<->@91:@;2- E>;80C;9-:019;:?@>-@1;853;/8;:-8 419-@;<;51?5? . . . .

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(297) RKH

(298) JK

(299) LLk

(300) .?P. :;. #'=J=D=J=J@1 6AEJ>ANC

(301) m'=HHI=NGOKB?=J?AN3DAJATPCAJAN=PEKJ

(302) n-33

(303) RKH

(304) JKLLk

(305) . :;. )+ >GKSEPV

(306) 2-"=PHEJ

(307) ,3,?"=HHEA

(308) =J@/&QPPKNL

(309) m$RE@AJ?APD=PPDAJQI>ANKB DAI=PKLKEAPE?OPAI?AHHOLAN=JEI=HEO?KJOANRA@EJI=II=HO

(310) n366,

(311) RKH

(312) JK

(313) LL k

(314) . :;. 2"=PHEJ

(315) +!QOMQA

(316) =J@1&=HA

(317) m3DANALHE?=PEKJN=PAKBDQI=JDAI=PKLKEAPE?OPAI?AHHOEJ RERK

(318) n366,

(319) RKH

(320) JK

(321) LLk

(322) . :;. 3)+AU

(323) $1,=N@EO

(324) +#EJC

(325) !%QHPKJ

(326) ,#,?+AHH=J

(327) *"DAJ

(328) ##KKHEJC

(329) !'#QJBKN@ 2DKNA

(330) 2,?&N=PD

(331) ,'E?GAJ>KPD=I

(332) +"KKG

(333) 1 >>KPP

(334) #$+=NOKJ

(335) #"*K>KH@P

(336) " /KDH

(337) 22IEPD

(338) '=SGEJO

(339) 2 >>KPP

(340) #+K?GA

(341) +6'EHHEAN

(342) 3,EJAN

(343) +%QHPKJ

(344) 5,=CNEJE

(345) 3 6UHEA

(346) )&H=OO?K?G

(347) )"KJUANO

(348) -2=J@AN

(349) 72DE

(350) )1.O>KNJA

(351) /,EJT

(352) #&KN@KJ

(353) "DEJS=HH=

(354) 89D=K

(355) 1$1EAO

(356) )$/=UPKJ

(357) /6AOPANRAHP

(358) ,'3KI=OOKJ

(359) ,6=POKJ

(360) ) !=PU

(361) )(R=JKRE?D

(362) 2'A=PD

(363) 6#2D=JJKJ

(364) 1-=C=N=F=J

(365) ,)6=HPAN

(366) #"+EJG

(367) 3 &N=Q>ANP

(368) )%#E/ANOEK

(369) =J@1*6EHOKJ

(370) m#- OAMQAJ?EJCKB=?UPKCAJAPE?=HHUJKNI=H=?QPA IUAHKE@HAQG=AIE=CAJKIA

(371) n):;8-

(372) RKH

(373) JK

(374) LLk

(375) -KR. :;. $1,=N@EO

(376) +#EJC

(377) #)#KKHEJC

(378) #$+=NOKJ

(379) ,#,?+AHH=J

(380) *"DAJ

(381) #"*K>KH@P

(382) 1 2%QHPKJ

(383) *##AHAD=QJPU

(384) 2#,?&N=PD

(385) + %QHPKJ

(386) #/+K?GA

(387) 5),=CNEJE

(388) 1, >>KPP

(389) 3+5E?GANU

(390) )21AA@

(391) )21K>EJOKJ

(392) 36UHEA

(393) 2,2IEPD

(394) +"=NIE?D=AH

(395) ), $H@NA@

(396) ""'=NNEO

(397) )6=HGAN

(398) )!/A?G

(399) %#Q

(400) %#QGAO

(401) &$2=J@ANOKJ

(402) , !NQIIAPP

(403) $"H=NG

(404) )%,?,E?D=AH

(405) 1),AUAN

(406) )*2?DEJ@HAN

(407) "2/KDH

(408) )66=HHEO

(409) 7 2DE

(410) ++EJ

(411) '2?DIE@P

(412) 83=JC

(413) "'=ELAG

(414) ,$6EA?DANP

(415) )5(RU

(416) )*=HE?GE

(417) &$HHEKPP

(418) 1$ 1EAO

(419) )$/=UPKJ

(420) /6AOPANRAHP

(421) ,'3KI=OOKJ

(422) , 6=POKJ

(423) )!=PU

(424) 2'A=PD

(425) 6# 2D=JJKJ

(426) 1-=C=N=F=J

(427) #"+EJG

(428) ,)6=HPAN

(429) 3 &N=Q>ANP

(430) )%#E/ANOEK

(431) 1*6EHOKJ

(432) =J@3)+AU

(433) m1A?QNNEJCIQP=PEKJOBKQJ@>UOAMQAJ?EJC=J=?QPAIUAHKE@HAQGAIE= CAJKIA

(434) n5/3-,

(435) RKH

(436) JK

(437) LLk

(438) 2AL. :;. . +#EJC

(439) 3)+AU

(440) #$+=NOKJ

(441) " ,EHHAN

(442) #"*K>KH@P

(443) )26AH?D

(444) )*1EP?DAU

(445) , 8KQJC

(446) 3+=ILNA?DP

(447) ,#,?+AHH=J

(448) )%,?,E?D=AH

(449) )66=HHEO

(450) "+Q

(451) #2DAJ

(452) "" '=NNEO

(453) #)#KKHEJC

(454) 12%QHPKJ

(455) ++%QHPKJ

(456) *"DAJ

(457) '2?DIE@P

(458) )*=HE?GE 5AEVAN

(459) 5) ,=CNEJE

(460) +"KKG

(461) 2#,?&N=PD

(462) 3+5E?GANU

(463) ,"6AJ@H

(464) 2'A=PD

(465) , 6=POKJ

(466) #" +EJG

(467) ,'3KI=OOKJ

(468) 6#2D=JJKJ

(469) )$/=UPKJ

(470) 2*QHG=NJE

(471) /6AOPANRAHP

(472) ,)6=HPAN

(473) 3 &N=Q>ANP

(474) $1,=N@EO

(475) 1*6EHOKJ

(476) =J@)%#E/ANOEK

(477) m"HKJ=HARKHQPEKJEJNAH=LOA@ =?QPAIUAHKE@HAQG=AIE=NARA=HA@>USDKHA CAJKIAOAMQAJ?EJC

(478) n):;8-

(479) RKH

(480) JK

(481) LLk

(482) )=J. . .

(483) "D=LPAN. :;. )26AH?D

(484) 3)+AU

(485) #"+EJG

(486) " ,EHHAN

(487) #$+=NOKJ

(488) #"*K>KH@P

(489) +#6=NPI=J

(490) 3+ +=ILNA?DP

(491) %+EQ

(492) )7E=

(493) "*=J@KPD

(494) 12%QHPKJ

(495) ,#,?+AHH=J

(496) #)#KKHEJC

(497) )66=HHEO

(498) *"DAJ

(499) ""'=NNEO

(500) '*2?DIE@P

(501) ),*=HE?GE 5AEVAN

(502) "+Q

(503) 09D=JC

(504) ++EJ

(505) ,# .p+=QCDHEJ

(506) )%,?,E?D=AH

(507) *##AHAD=QJPU

(508) + %QHPKJ

(509) 5),=CNEJE

(510) 2#,?&N=PD

(511) 13 #AIAPAN

(512) 3+5E?GANU

(513) )'QJ@=H

(514) ++"KKG

(515) &62SEBP

(516) )/1AA@

(517) / HH@NA@CA

(518) 3- 6UHEA

(519) )16=HGAN

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