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Whole Genome Sequencing

Germline genetics within the SJLIFE cohort has been conducted using DNA extracted from blood samples for survivors and cancer-free controls, which include the following:

  • SNP genotyping for 2,534 survivors using Affymetrix array 6.0.
  • Whole-genome sequencing (WGS) with 30X coverage was performed at the HudsonAlpha Institute for 4402 survivors and 447 non-cancer controls (3006 survivors and 341 controls using Illumina HiSeq X Ten sequencers; 1,396 survivors and 106 controls using Illumina NovaSeq).
  • Whole-exome sequencing (WES) with 100X coverage was performed at SJCRH for the 4422 survivors and 447 non-cancer controls using Illumina HiSeq 4000 platform and the Illumina NovaSeq.
  • Primary sequencing data analysis including quality control, mapping and variant calling was carried through an automated pipeline by the bioinformatics team in the Department of Computation Biology at St. Jude Children's Research Hospital, resulting in a WGS/WES clean data set. While 4,402 survivor samples were sent for whole genome sequencing, numerous samples failed to contribute to a curated database of completely sequenced genomes. The reasons varied and included bacterial contamination, excess heterozygosity, sex discordance, quality control failure, or a combination of those. The pipeline yielded 4382 survivor blood samples/genomes available for analysis via the St. Jude Cloud.

Genomics characterization, genome-wide epigenetic profiling was done, as a pilot study, for a subset of 300 survivors using Illumina MethylationEPIC BeadChip.


 

Characteristics Breakdown N (%)
Sex Female 2080 (47.5)
Male 2302 (52.5)
Race White 3569 (81.5)
Black 703 (16.0)
Other 110 (2.5)
Hispanic Ethnicity Yes 136 (3.1)
No 4246 (96.9)
Primary Diagnosis Acute lymphoblastic leukemia 1254 (28.7)
Acute myeloid leukemia 138 (3.2)
Other leukemia 7 (0.2)
Other hematologic malignancy 33 (0.7)
CNS tumor 645 (14.7)
Ewing sarcoma family of tumors 118 (2.7)
Osteosarcoma 155 (3.5)
Germ cell tumor 95 (2.2)
Hepatoblastoma 26 (0.6)
Hodgkin lymphoma 464 (10.6)
Non-Hodgkin lymphoma 280 (6.4)
Melanoma 41 (0.9)
Neuroblastoma 217 (4.9)
Retinoblastoma 259 (5.9)
Rhabdomyosarcoma  148 (3.4)
Non-Rhabdomyosarcoma  125 (3.4)
Wilms tumor  274 (6.3)
Carcinomas 61 (1.4)
Other malignancy 28 (0.6)
Other neoplasm  14 (0.3)
Age at Diagnosis (Years) Mean +/- sd 7.7 +/- 5.6
Median 6.3
Range 0 – 23
<1 386 (8.8)
1 - 4 1489 (34.0)
5 - 9 954 (21.8)
10 - 14 902 (20.6)
15 - 19 619 (14.1)
20 - 23 32 (0.7)
Diagnosis to Baseline Visit or Expansion Consent (Years) Mean +/- sd 22.5 +/- 10.8
Median 20.8
Range 5 – 55
5 - 9 532 (12.1)
10 - 19 1550 (35.4)
20 - 29 1159 (26.5)
30 - 39 822 (18.8)
40 - 49 296 (6.8)
50-59 23 (0.5)
Age at Baseline Visit or Expansion Consent (Years) Mean +/- sd 27.5 +/- 10.0
Median 26.1
Range 6 – 64
<18 712 (16.3)
18 - 24 1273 (29.1)
25 - 29 781 (17.8)
30 - 34 653 (14.9)
35 - 39 432 (9.9)
40 - 44 284 (6.5)
45 - 49 159 (3.6)
50 - 64 88 (2.0)

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