APPENDICES
This appendices section provides details and descriptions of the analyses and data provided in the tumour genome report. Look here for specifics on how the analyses were run, glossaries of unfamiliar terms and references to specific protocols and analysis pipelines.
APPENDIX A
SAMPLE INFORMATION
Sample Sample Name Collection Date Primary Site Biopsy Site Pathology Estimated Tumour Content
Constitutional POG098-PB 04-16-14 Blood-Peripheral Normal tissue na
Tumour POG098-OCT-1 05-06-14 Bone-Vertebra spinal mass 65%
SEQUENCING QC
Type Sample Name Input (ng) Library Construction Protocol Library Lac QC Sequencing QC % Duplicates Total Coverage # Reads
Constitutional DNA POG098-PB 1000.0 WGS P00157 Approved Passed 1.8 63X na
Tumour RNA POG098-OCT-1 3672.0 RNA P00163 Approved Passed na na 58M
Tumour DNA POG098-OCT-1 1000.0 WGS P00159 Approved Passed 2.29 106X na
APPENDIX B
TCGA ACRONYM
Code Name Full Name Data Source Tumour Count Normal Count
ACC Adrenocortical Carcinoma TCGA 79 0
BLCA Urothelial Bladder Carcinoma TCGA 408 19
BRCA Breast Ductal Carcinoma TCGA 1095 113
BRCA_BL Basal Breast Carcinoma Subtype TCGA 136 16
BRCA_ER_Negative ER - Breast Carcinoma TCGA 236 21
BRCA_ER_Negative_PR_Negative_HER2_Negative ER-/PR-/HER2- Breast Carcinoma TCGA 115 11
BRCA_ER_Negative_PR_Negative_HER2_Positive ER-/PR-/HER2+ Breast Carcinoma TCGA 37 4
BRCA_ER_Negative_PR_Positive_HER2_Negative ER-/PR+/HER2- Breast Carcinoma TCGA 8 0
BRCA_ER_Negative_PR_Positive_HER2_Positive ER-/PR+/HER2+ Breast Carcinoma TCGA 2 1
BRCA_ER_Positive ER + Breast Carcinoma TCGA 806 79
BRCA_ER_Positive_PR_Negative_HER2_Negative ER+/PR-/HER2- Breast Carcinoma TCGA 65 7
BRCA_ER_Positive_PR_Negative_HER2_Positive ER+/PR-/HER2+ Breast Carcinoma TCGA 23 2
BRCA_ER_Positive_PR_Positive_HER2_Negative ER+/PR+/HER2- Breast Carcinoma TCGA 369 37
BRCA_ER_Positive_PR_Positive_HER2_Positive ER+/PR+/HER2+ Breast Carcinoma TCGA 100 15
BRCA_H2 HER2 Breast Carcinoma TCGA 65 9
BRCA_HER2_Negative HER2- Breast Carcinoma TCGA 561 56
BRCA_HER2_Positive HER2+ Breast Carcinoma TCGA 162 22
BRCA_LA Luminal A Breast Carcinoma TCGA 415 57
BRCA_LB Luminal B Breast Carcinoma TCGA 176 21
BRCA_NL Normal-like Breast Carcinoma TCGA 25 2
BRCA_PR_Negative PR- Breast Carcinoma TCGA 343 31
BRCA_PR_Positive PR+ Breast Carcinoma TCGA 696 69
CESC Cervical Squamous Cell Carcinoma and
Endocervical Adenocarcinoma
TCGA 0 0
CESC_CAD Cervical Squamous Cell Carcinoma and
Endocervical Adenocarcinoma
TCGA 47 1
CESC_SCC Cervical Squamous Cell Carcinoma and
Endocervical Adenocarcinoma
TCGA 257 2
CHOL Cholangiocarcinoma TCGA 36 9
COADREAD Colorectal Adenocarcinoma TCGA 372 51
DLBC Diffuse Large B-Cell Lymphoma/Lymphoid
Neoplasm Diffuse Large B-cell Lymphoma
TCGA 48 0
DLBC_BM DLBCL Blood/Bone Marrow BCGSC 11 0
DLBC_CB DLBCL CEntroblasts BCGSC 0 20
DLBC_CL DLBCL Cell lines BCGSC 35 0
ESCA Esophageal carcinoma TCGA 15 1
ESCA_EAC Esophageal carcinoma TCGA 79 8
ESCA_SCC Esophageal carcinoma TCGA 90 2
FL Follicular Lymphoma BCGSC 50 0
GBM Glioblastoma Multiforme TCGA 161 5
HNSC Head and Neck Squamous Cell Carcinoma TCGA 520 44
KICH Chromophobe Renal Cell Carcinoma/
Kidney Chromophobe
TCGA 66 25
LAML Acute Myeloid Leukemia TCGA 173 0
LCML Chronic Myelogenous Leukemia TCGA NA NA
LGG Lower Grade Glioma TCGA 516 0
LIHC Liver Hepatocellular Carcinoma TCGA 371 50
LUAD Lung Adenocarcinoma TCGA 515 59
LUSC Lung Squamous cell Carcinoma TCGA 501 50
MB-Adult Brain MAGIC 143 0
MB-Infant Medulloblastoma MAGIC NA NA
MB-Pediatric Medulloblastoma MAGIC NA NA
MESO Mesothelioma TCGA 87 0
NBL Neuroblastoma TCGA 0 0
NCI_GPH_DLBCL Diffuse Large B-Cell Lymphoma/Lymphoid
Neoplasm Diffuse Large B-cell Lymphoma
TCGA 111 0
OV Ovarian Serous Cystadenocarcinoma TCGA 305 0
PAAD Pancreatic Ductal Adenocarcinoma TCGA 178 0
PCPG Paraganglioma & Pheochromocytoma TCGA 179 3
POG-pediatric POG Pediatric POG NA NA
PRAD Prostate Adenocarcinoma TCGA 497 52
RHBD Rahbdoid TCGA 0 0
SARC Sarcoma TCGA 259 2
SARC_DDL Dedifferentiated Liposarcoma TCGA 57 1
SARC_desmoid Desmoid Tumour TCGA 2 0
SARC_LMS Leiomyosarcoma TCGA 104 1
SARC_MFS Myxofibrosarcoma TCGA 25 0
SARC_MPNST Malignant Peripheral Nerve Sheath Tumors TCGA 9 0
SARC_Synovial Synovial Sarcoma TCGA 9 0
SARC_UPS Undifferentiated pleomorphic sarcoma TCGA 20 0
SKCM Cutaneous Melanoma TCGA 469 1
STAD Stomach Adenocarcinoma TCGA 415 35
STAD_CIN Stomach Adenocarcinoma Chromosomal
Instability
TCGA 138 16
STAD_EBV Stomach Adenocarcinoma Epstein-Barr
virus positive
TCGA 25 1
STAD_GS Stomach Adenocarcinoma Genomically
Stable
TCGA 54 6
STAD_MSI Stomach Adenocarcinoma Microsatellite TCGA 60 7
TFRI_GBM_cell_line TFRI GBM Cell Line TCGA NA NA
TFRI_GBM_CL TFRI GBM Cell Line TFRI 67 0
TFRI_GBM_NCL TFRI GBM Non Cell Line TFRI 52 0
TGCT Testicular Germ Cell Cancer TCGA 150 0
THCA Papillary Thyroid Carcinoma/Thyroid
Carcinoma
TCGA 505 59
THYM Thymoma TCGA 120 2
UCEC Uterine Corpus Endometrial Carcinoma TCGA 177 24
UCS Uterine Carcinosarcoma TCGA 57 0
UVM Uveal Melanoma TCGA 80 0
APPENDIX C
REPORT OVERVIEW

The Tumour Genome Analysis report provides a comprehensive description of the somatic genetic alterations present in a tumour. All genes in the genome are assessed for alterations of all types, including substitutions, deletions, gene fusions, amplification, and overexpression. Both known and novel alterations which affect genes of potential clinical relevance are included in the report. Germline variants are not generally included in the report.

The Tumour Genome Analysis report is developed by Canada's Michael Smith Genome Sciences Centre, part of the BC Cancery Agency. Contents should be regarded as purely investigational and are intended for research purposes only

METHODS OVERVIEW

The complete report is based on whole genome sequencing of tumour and matched normal DNA, and whole transcriptome sequencing of tumour RNA. Tumour and normal sequences are compared to the reference human genome to identify tumour-specific alterations including single nucleotide variants, small insertions and deletions, copy number changes, and structural variants such as translocations. Sequences are also assembled in a reference-independent manner to identify further structural alterations. Additionally, RNA sequences are used to measure expression of all genes, and genes with over and under-expression compared to reference tissues are identified. Somatic changes are cross-referenced to databases of therapeutic, diagnostic, prognostic, and biological information, pinpointing the alterations most likely to have clinical relevance. This comprehensive tumour description is expert reviewed by a Genome Analyst, highlighting potential driver mutations, providing pathway context, interpreting results in tumour type context, and refining potential therapeutic targets.

DETAILED METHODS

Genome status: Tumour content and ploidy are determined based on expert review of copy number and allelic ratios observed across all chromosomes in the tumour.

Tissue comparators and expression comparisons: The most appropriate normal tissue and tumour tissues are chosen for expression comparisons based on the tumour type and observed correlation with tissue data sets. If no appropriate tissue comparator is available, for instance for rare tumours, an average across all tissues is used. Fold change in expression is calculated compared to the normal tissue, and percentile expression is calculated compared to all tumour samples of that disease type. Outlier expression refers to genes with very high or very low expression compared to what is seen in other cancers of that type.

Microbial content: Sequences are compared to databaes of viral, bacterial and fungal sequences in addition to the human genome. The microbial species is reported if observed levels are suggestive of microbial presence in the tumour sample. Specific viral integration sites are reported if identified in genomic DNA sequence.

Mutation burden: The number of protein coding alterations of each type, including both known and novel events, are totaled and compared to other tumours of a similar type. For SNVs and indels, this includes data from TCGA, while for structural variants, comparisons are only made among POG samples due to differences in how these variants are identified in TCGA.

Key genomic and transcriptomic alterations: The subset of alterations which have a previously described effect on genes of clinical or biological significance are summarized, with details of significance provided in the Detailed Genomic Analysis section, and details of the exact alteration provided in the section of the report corresponding to that mutation type. Additional alterations in these genes, which have not been previously observed and do not have an inferred functional effect, are variants of uncertain significance (VUS), and are only listed in the subsequent sections of the report. Alterations in genes which are not associated with cancer, cancer pathways, or therapeutics, are not usually included in the genomic report but are available upon request to the Genome Sciences Centre.

Genomic events with potential therapeutic association: The subset of alterations with specific therapeutic associations are identified using the Genome Sciences Centre's curated Knowledgebase, which integrates information from sources including cancer databases, drug databases, clinical tests, and the literature. Associations are listed by the level of evidence for the use of that drug in the context of the observed alteration, including those that are approved in this or other cancer types, and those that have early clinical or preclinical evidence.