The Children’s Oncology Group and QuadW Foundation ... 2013/ASCO 2013 Osteosarcoma... · Fig 1....
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Fig 1. Patient accrual to the Osteosarcoma Biology studies (P9851 and ASOT 06B1) has proceeded at or above expectations. The Children’s Oncology Group and QuadW Foundation Osteosarcoma Banking Experience J.M. Glover, R.G. Gorlick, D.A. Barkauskas and C. Khanna Abstract: Background: Survival rates of osteosarcoma patients have remained stagnant over the last twenty years. Predictive biomarkers of response to treatment and likelihood of recurrence are yet to be developed. In order to develop new therapeutics and better risk-stratified regimens, a greater understanding of osteosarcoma biology is needed. The Children’s Oncology Group (COG) addressed this need by banking more than 10,000 tumor and tissue samples from over 1500 patients with osteosarcoma, but many samples lacked clinically relevant data. Methods: 1105 eligible patients enrolled on the COG osteosarcoma biology study P9851. Of those, 510 patients were not enrolled on a concurrent therapeutic trial, which limited the clinical annotation of those samples. 589 patients have enrolled on the successor study AOST06B1. The lack of clinical annotation of the P9851 specimens limited their value, and the lack of statistical support slowed the analysis of several biology studies. The QuadW Foundation, CureSearch, and the COG formed the Childhood Sarcoma Biostatistics and Annotation Office (CSBAO) in 2008 to link clinically annotated patient data to the samples and to provide statistical support. Results: In 2008, only 5.3% of samples from the 510 P9851 patients not enrolled on a therapeutic study had full clinical annotation. The efforts of the CSBAO have linked clinical annotation to 90.8% of those specimens and provided statistical analyses. As a result, 27 biology studies in osteosarcoma are completed, with 23 published in peer-reviewed journals. Samples were provided to the TARGET program (for gene expression arrays, copy number analysis, and sequencing data); the resulting data will be available to the scientific community for in silico studies. Conclusions: The efforts of the CSBAO have led to a substantial increase in the value of a large osteosarcoma biospecimen repository by clinically annotating the specimens and providing statistical resources for analyses of planned and completed studies. These samples with annotated patient information are available by request to the research community for basic and translational science projects to improve the biological understanding of, and the treatment of patients with osteosarcoma. Background: Osteosarcoma is the most common malignant bone tumor diagnosed in children. There are about 400 new pediatric and adolescent patients with this diagnosis per year in the US. Current treatment that provides patients with the greatest opportunity for survival osteosarcoma involves multidisciplinary treatment with both surgery and chemotherapy. The chemotherapeutic regimens used are long and intensive including cisplatin, doxorubicin, and high dose methotrexate with or without ifosfamide, and etoposide. These agents have a high incidence of acute and late side effects including cardiotoxicity, hearing loss, decreased fertility, and development of a secondary malignancy. We are at the beginnings of understanding what genetic drivers play a part in osteosarcoma oncogenesis in relation to other sarcomas. Unlike Ewing Sarcoma, the second most common bone tumor in children, which has a balanced karyotype with the uniform reciprocal translocation (EWS/FLI1), osteosarcoma appears to be a much more heterogeneous disease with complex karyotypes.[4] The known genetic mutations associated with osteosarcoma include the P53 gene associated with Li Fraumeni Syndrome, the RB1 tumor suppressor gene associated with hereditary retinoblastoma, BLM gene seen in Bloom syndrome, and RECQL4 gene associated with Rothmund Thomson syndrome. In this age of personalized medicine we need to understand the genetic mechanisms of osteosarcoma to develop druggable targets, overcome resistance to therapy, and prognosticate and risk stratify patient’s treatments. Results: P9851 was open for 3218 days (8.82 years), which should yield 3528 expected cases of pediatric osteosarcoma. P9851 collected samples from 1105 patients or (31%) of the expected cases of pediatric osteosarcoma. At the time of last data freeze and analysis AOST06B1 has been open for 1938 days (5.3 years) which yields 2120 expected cases. So far it has enrolled 621 patients with osteosarcoma or 29.3% of the expected pediatric osteosarcoma population. 27 biology projects have been completed using samples from P9851 or AOST06B1, of those 23 have published in peer reviewed journals. Additionally, one of the successes of the CSBAO has been to help move 7 osteosarcoma biology projects into publication by providing biostatistical support (Table 1) . The Children’s Oncology Group, the Quad W Foundation, and Curesearch recognized that many samples in the biorepository lacked clinically linked data, and the overall value of the repository was diminished. Additionally there was no biostatistical support available to basic and translational projects from the osteosarcoma repository that stagnated their publication. To address these problems the Childhood Sarcoma Biostatistics and Annotation Office (CSBAO) was created to provide the following infrastructure: 1.Management of clinical annotation for all patient samples held in the osteosarcoma repository (including validation of clinical annotation quality and completeness). 2.Review and aid in completion of statistical technical reports for biology and other osteosarcoma-related projects. 3.Distribution and integration of clinical data for osteosarcoma biology projects that have completed biological analysis by use of a high dimensional database (HDD) for osteosarcoma. 4.Use of a new platform to manage biospecimen requests for Osteosarcoma and Ewing Sarcoma. 5.Initiation of Ewing’s Sarcoma and Soft Tissue Sarcoma biology projects. 6.Development of a standard operating procedure (SOP) for collecting quality specimens for AOST06B1. The CSBAO worked with all of the treating institutions that had patients lacking clinically annotated data in order to recover critical information. Conclusions: •As a result of the COG, QuadW foundation and the CSBAO efforts of the two osteosarcoma banking studies, the world’s largest tumor bank of osteosarcoma samples with clinically linked data has been collected. •The value the COG Osteosarcoma Biospecimen Repository has been increased significantly by the efforts of the CSBAO by obtaining missing clinical annotation. •Our goal is to continue to provide high quality specimens of tumor and related tissue samples as well as biostatistical support to qualified researchers with projects that advance the understanding and treatment of patients with osteosarcoma. •A future direction for the COG Osteosarcoma Biospecimen Repository will be to link biological data generated by investigators to the physical and clinical data for banked samples. •We have begun to collect this data into a High Dimensional Database (HDD) that will be available for qualified researchers to conduct in silico studies. •Eventually we expect the HDD to contain information including ErbB-2, Chromosomal Instability, Telomerase Activity, Fas Expression, IGF-1 and IGF1R assays and SPECS gene expression data, genome wide association study data, and array data from the TARGET project. •The next direction the CSBAO will take is to expand its efforts to aid in other childhood sarcomas, most recently Ewing sarcoma and soft tissue sarcoma, including rhabdomyosarcoma. Methods: The Children’s Oncology Group recognized the need to better understand biology of osteosarcoma to improve outcome began in the late 1990’s. Indeed, to accomplish this a biospecimen repository was established with the goal of having each sample linked to clinically annotated information and patient outcome. Since that time two studies have enrolled patients with osteosarcoma to collect patient samples for translational research, each is described below: P9851 Osteosarcoma Biology Protocol: Companion to Group-Wide Therapeutic Studies P9851 was a biology study with the intention to increase the knowledge of the basic osteosarcoma biology for the discovery of novel therapeutic targets, as well as to determine biologic prognostic indicators and biomarkers that could be predictive of outcome. P9851 enrolled 1110 (1105 eligible) patients from 211 COG institutions from 1999 to 2008. During the time that P9851 was accruing patients there were periods when there was no open accompanying treatment study for patients with localized or metastatic disease. Additionally, the requirement for clinical follow up and data tracking was not clear for patients not enrolled on a treatment study. Although 5,369 tissue and tumor samples were collected on 1105 patients, about half of the patients enrolled on P9851 were not enrolled on accompanying treatment study. The majority of these patients had no clinically linked follow up data, so only a fraction of the available clinical data was collected. This severely hampered the value of the bank tumor bank. Publications produced from samples collected on P9851 Journal Biology of childhood osteogenic sarcoma and potential targets for therapeutic development: meeting summary Clin Cancer Res. 2003 Nov 15;9(15):5442-53. The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis. Nat Med. 2004 Jan 4 Epub 2004 Jan 04 Determination of a minimal region of loss of heterozygosity on chromosome 18q21.33 in osteosarcoma Int J Cancer. 2003 Jun 10;105(2):285-8. Sequence alterations in the reduced folate carrier are observed frequently in osteosarcoma tumor samples Clin Cancer Res 2003; 9:837-844. Dependence of osteosarcoma metastasis on ezrin, a membrane-cytoskeleton linker protein Proc AACR 2002;43:1066 [abstract]. Promoter methylation may influence expression of the reduced folate carrier. Proc AACR 2003;44:598 [abstract]. Polymorphisms in the 3’ untranslated region of the reduced folate carrier and their correlation with mRNA expression in osteosarcoma Proc AACR 2003;44:139 [abstract]. Ezrin a cell membrane cytoskeletal linker protein is necessary for osteosarcoma pulmonary metastasis Proc ASCO 2003;22:3449 [abstract]. PHC3, a component of the hPRC-H complex, associates with E2F6 during G(0) and is lost in osteosarcoma tumors Oncogene 2007;26:1714-22. Epub Sep 2006. Wnt/LRP5 signaling by a soluble receptor modulates the epithelial to mesenchymal transition and suppresses met and metalloproteinases in osteosarcoma Saos-2 cells J Orthop Res. 2007;25:964-971. Epub Feb 2007. Multiple Drug Resistance in Osteogenic Sarcoma (INT0133) J Clin Oncol 2007;25:2057-2062. Over-expression of parathyroid hormone type 1 receptor confers an aggressive phenotype in osteosarcoma Int J Cancer. 2007;121:943-954. Epub April 2007. The folate receptor alpha is frequently over-expressed in osteosarcoma samples and plays a role in the uptake of the physiological substrate, 5-methyl-tetrahydrofolate Clin Cancer Res 2007;13:2557-2567 Platelet-derived growth factor receptor as a prognostic marker and a therapeutic target for imatinib mesylate therapy in osteosarcoma Cancer. 2008;112:2119-2129. Epub Mar 2008. Quantitative correlation between promoter methylation and messenger RNA levels of the reduced folate carrier BMC Cancer. 2008;8:124. Hypoxia markers in human osteosarcoma: An exploratory study Clin Orthop Related Res. Epub Jun 2008. Polymorphisms and methylation of the reduced folate carrier in osteosarcoma Clin Orthop Related Res. Epub Jun 2008. Cell cycle regulator gene CDC5L, a potential target for 6p12-p21 amplicon in osteosarcoma Cancer Res. 2008;6:937-946 Blocking Wnt/LRP5 signaling by a soluble receptor modulates the epithelial to mesenchymal transition and suppresses met and metalloproteinases in osteosarcoma Saos-2 cells J Orthop Res. 2007 Jul;25(7):964-71. The actin-cytoskeleton linker protein ezrin is regulated during osteosarcoma metastasis by PKC Oncogene. 2009; 28: 792-802. Epub Dec 2008 Publications produced with assistance from the CSBAO Journal Investigation of the insulin-like growth factor-1 signaling pathway in localized Ewing sarcoma. Cancer 117(21): 4966– 4976. Detectable clonal mosaicism and its relationship to aging and cancer. Nature Genetics 44(6): 651–658. Poor Survival for Osteosarcoma of the Pelvis: A Report from the Children’s Oncology Group. . Clinical Orthopaedics and Related Research 470(7): 2007–2013 Phase II Trial of Trastuzumab in Combination With Cytotoxic Chemotherapy for Treatment of Metastatic Osteosarcoma With Human Epidermal Growth Factor Receptor 2 Overexpression: A Report From the Children's Oncology Group. JCO 30(20): 2545– 2551. Outcome for adolescent and young adult patients with osteosarcoma. Cancer 118(18): 4597– 4605 Publications accepted with assistance from the CSBAO Journal Chemotherapy-associated Toxicities in Overweight and Underweight Children with Osteosarcoma PBC Genome-wide Association Study Identifies Novel Loci Associated with Osteosarcoma Nature Genetics Fig 2. Successful clinically annotation for the majority of patients represented in the osteosarcoma biospecimen repository. A substantial limitation to the use of this biospecimen repository was that only 5.3% of samples from patients not enrolled on a therapeutic studies had full clinical annotation. As a result of efforts of the CSBAO, 90.8% these patient samples are now linked to clinical annotation. Fig 3. Sample of tissue microarrays that are available to researchers. There are 52 patient sample on the array as well as 10 healthy tissues (adrenal breast and tonsil) as controls. 38 of the 52 samples have clinically annotated data available. One of the patients on the array had osteosarcoma following treatment for acute leukemia and is considered a secondary malignancy.
Transcript of The Children’s Oncology Group and QuadW Foundation ... 2013/ASCO 2013 Osteosarcoma... · Fig 1....
Fig 1. Patient accrual to the Osteosarcoma Biology studies (P9851 and ASOT 06B1) has proceeded at or above expectations.
The Children’s Oncology Group and QuadW Foundation Osteosarcoma Banking Experience J.M. Glover, R.G. Gorlick, D.A. Barkauskas and C. Khanna
Abstract: Background: Survival rates of osteosarcoma patients have remained stagnant over the last twenty years. Predictive biomarkers of response to treatment and likelihood of recurrence are yet to be developed. In order to develop new therapeutics and better risk-stratified regimens, a greater understanding of osteosarcoma biology is needed. The Children’s Oncology Group (COG) addressed this need by banking more than 10,000 tumor and tissue samples from over 1500 patients with osteosarcoma, but many samples lacked clinically relevant data. Methods: 1105 eligible patients enrolled on the COG osteosarcoma biology study P9851. Of those, 510 patients were not enrolled on a concurrent therapeutic trial, which limited the clinical annotation of those samples. 589 patients have enrolled on the successor study AOST06B1. The lack of clinical annotation of the P9851 specimens limited their value, and the lack of statistical support slowed the analysis of several biology studies. The QuadW Foundation, CureSearch, and the COG formed the Childhood Sarcoma Biostatistics and Annotation Office (CSBAO) in 2008 to link clinically annotated patient data to the samples and to provide statistical support. Results: In 2008, only 5.3% of samples from the 510 P9851 patients not enrolled on a therapeutic study had full clinical annotation. The efforts of the CSBAO have linked clinical annotation to 90.8% of those specimens and provided statistical analyses. As a result, 27 biology studies in osteosarcoma are completed, with 23 published in peer-reviewed journals. Samples were provided to the TARGET program (for gene expression arrays, copy number analysis, and sequencing data); the resulting data will be available to the scientific community for in silico studies. Conclusions: The efforts of the CSBAO have led to a substantial increase in the value of a large osteosarcoma biospecimen repository by clinically annotating the specimens and providing statistical resources for analyses of planned and completed studies. These samples with annotated patient information are available by request to the research community for basic and translational science projects to improve the biological understanding of, and the treatment of patients with osteosarcoma.
Background: Osteosarcoma is the most common malignant bone tumor diagnosed in children. There are about 400 new pediatric and adolescent patients with this diagnosis per year in the US. Current treatment that provides patients with the greatest opportunity for survival osteosarcoma involves multidisciplinary treatment with both surgery and chemotherapy. The chemotherapeutic regimens used are long and intensive including cisplatin, doxorubicin, and high dose methotrexate with or without ifosfamide, and etoposide. These agents have a high incidence of acute and late side effects including cardiotoxicity, hearing loss, decreased fertility, and development of a secondary malignancy. We are at the beginnings of understanding what genetic drivers play a part in osteosarcoma oncogenesis in relation to other sarcomas. Unlike Ewing Sarcoma, the second most common bone tumor in children, which has a balanced karyotype with the uniform reciprocal translocation (EWS/FLI1), osteosarcoma appears to be a much more heterogeneous disease with complex karyotypes.[4] The known genetic mutations associated with osteosarcoma include the P53 gene associated with Li Fraumeni Syndrome, the RB1 tumor suppressor gene associated with hereditary retinoblastoma, BLM gene seen in Bloom syndrome, and RECQL4 gene associated with Rothmund Thomson syndrome. In this age of personalized medicine we need to understand the genetic mechanisms of osteosarcoma to develop druggable targets, overcome resistance to therapy, and prognosticate and risk stratify patient’s treatments.
Results: P9851 was open for 3218 days (8.82 years), which should yield 3528 expected cases of pediatric osteosarcoma. P9851 collected samples from 1105 patients or (31%) of the expected cases of pediatric osteosarcoma. At the time of last data freeze and analysis AOST06B1 has been open for 1938 days (5.3 years) which yields 2120 expected cases. So far it has enrolled 621 patients with osteosarcoma or 29.3% of the expected pediatric osteosarcoma population. 27 biology projects have been completed using samples from P9851 or AOST06B1, of those 23 have published in peer reviewed journals. Additionally, one of the successes of the CSBAO has been to help move 7 osteosarcoma biology projects into publication by providing biostatistical support (Table 1) .
The Children’s Oncology Group, the Quad W Foundation, and Curesearch recognized that many samples in the biorepository lacked clinically linked data, and the overall value of the repository was diminished. Additionally there was no biostatistical support available to basic and translational projects from the osteosarcoma repository that stagnated their publication. To address these problems the Childhood Sarcoma Biostatistics and Annotation Office (CSBAO) was created to provide the following infrastructure: 1.Management of clinical annotation for all patient samples held in the osteosarcoma repository (including validation of clinical annotation quality and completeness).
2.Review and aid in completion of statistical technical reports for biology and other osteosarcoma-related projects.
3.Distribution and integration of clinical data for osteosarcoma biology projects that have completed biological analysis by use of a high dimensional database (HDD) for osteosarcoma.
4.Use of a new platform to manage biospecimen requests for Osteosarcoma and Ewing Sarcoma.
5.Initiation of Ewing’s Sarcoma and Soft Tissue Sarcoma biology projects.
6.Development of a standard operating procedure (SOP) for collecting quality specimens for AOST06B1.
The CSBAO worked with all of the treating institutions that had patients lacking clinically annotated data in order to recover critical information.
Conclusions: •As a result of the COG, QuadW foundation and the CSBAO efforts of the two osteosarcoma banking studies, the world’s largest tumor bank of osteosarcoma samples with clinically linked data has been collected. •The value the COG Osteosarcoma Biospecimen Repository has been increased significantly by the efforts of the CSBAO by obtaining missing clinical annotation. •Our goal is to continue to provide high quality specimens of tumor and related tissue samples as well as biostatistical support to qualified researchers with projects that advance the understanding and treatment of patients with osteosarcoma. •A future direction for the COG Osteosarcoma Biospecimen Repository will be to link biological data generated by investigators to the physical and clinical data for banked samples. •We have begun to collect this data into a High Dimensional Database (HDD) that will be available for qualified researchers to conduct in silico studies. •Eventually we expect the HDD to contain information including ErbB-2, Chromosomal Instability, Telomerase Activity, Fas Expression, IGF-1 and IGF1R assays and SPECS gene expression data, genome wide association study data, and array data from the TARGET project. •The next direction the CSBAO will take is to expand its efforts to aid in other childhood sarcomas, most recently Ewing sarcoma and soft tissue sarcoma, including rhabdomyosarcoma.
Methods: The Children’s Oncology Group recognized the need to better understand biology of osteosarcoma to improve outcome began in the late 1990’s. Indeed, to accomplish this a biospecimen repository was established with the goal of having each sample linked to clinically annotated information and patient outcome. Since that time two studies have enrolled patients with osteosarcoma to collect patient samples for translational research, each is described below: P9851 Osteosarcoma Biology Protocol: Companion to Group-Wide Therapeutic Studies P9851 was a biology study with the intention to increase the knowledge of the basic osteosarcoma biology for the discovery of novel therapeutic targets, as well as to determine biologic prognostic indicators and biomarkers that could be predictive of outcome. P9851 enrolled 1110 (1105 eligible) patients from 211 COG institutions from 1999 to 2008. During the time that P9851 was accruing patients there were periods when there was no open accompanying treatment study for patients with localized or metastatic disease. Additionally, the requirement for clinical follow up and data tracking was not clear for patients not enrolled on a treatment study. Although 5,369 tissue and tumor samples were collected on 1105 patients, about half of the patients enrolled on P9851 were not enrolled on accompanying treatment study. The majority of these patients had no clinically linked follow up data, so only a fraction of the available clinical data was collected. This severely hampered the value of the bank tumor bank.
Publications produced from samples collected on P9851 Journal
Biology of childhood osteogenic sarcoma and potential targets for therapeutic development: meeting summary
Clin Cancer Res. 2003 Nov 15;9(15):5442-53.
The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis.
Nat Med. 2004 Jan 4 Epub 2004 Jan 04
Determination of a minimal region of loss of heterozygosity on chromosome 18q21.33 in osteosarcoma
Int J Cancer. 2003 Jun 10;105(2):285-8.
Sequence alterations in the reduced folate carrier are observed frequently in osteosarcoma tumor samples
Clin Cancer Res 2003; 9:837-844.
Dependence of osteosarcoma metastasis on ezrin, a membrane-cytoskeleton linker protein
Proc AACR 2002;43:1066 [abstract].
Promoter methylation may influence expression of the reduced folate carrier.
Proc AACR 2003;44:598 [abstract].
Polymorphisms in the 3’ untranslated region of the reduced folate carrier and their correlation with mRNA expression in osteosarcoma
Proc AACR 2003;44:139 [abstract].
Ezrin a cell membrane cytoskeletal linker protein is necessary for osteosarcoma pulmonary metastasis
Proc ASCO 2003;22:3449 [abstract].
PHC3, a component of the hPRC-H complex, associates with E2F6 during G(0) and is lost in osteosarcoma tumors
Oncogene 2007;26:1714-22. Epub Sep 2006.
Wnt/LRP5 signaling by a soluble receptor modulates the epithelial to mesenchymal transition and suppresses met and metalloproteinases in osteosarcoma Saos-2 cells
J Orthop Res. 2007;25:964-971. Epub Feb 2007.
Multiple Drug Resistance in Osteogenic Sarcoma (INT0133)
J Clin Oncol 2007;25:2057-2062.
Over-expression of parathyroid hormone type 1 receptor confers an aggressive phenotype in osteosarcoma
Int J Cancer. 2007;121:943-954. Epub April 2007.
The folate receptor alpha is frequently over-expressed in osteosarcoma samples and plays a role in the uptake of the physiological substrate, 5-methyl-tetrahydrofolate
Clin Cancer Res 2007;13:2557-2567
Platelet-derived growth factor receptor as a prognostic marker and a therapeutic target for imatinib mesylate therapy in osteosarcoma
Cancer. 2008;112:2119-2129. Epub Mar 2008.
Quantitative correlation between promoter methylation and messenger RNA levels of the reduced folate carrier
BMC Cancer. 2008;8:124.
Hypoxia markers in human osteosarcoma: An exploratory study
Clin Orthop Related Res. Epub Jun 2008.
Polymorphisms and methylation of the reduced folate carrier in osteosarcoma
Clin Orthop Related Res. Epub Jun 2008.
Cell cycle regulator gene CDC5L, a potential target for 6p12-p21 amplicon in osteosarcoma
Cancer Res. 2008;6:937-946
Blocking Wnt/LRP5 signaling by a soluble receptor modulates the epithelial to mesenchymal transition and suppresses met and metalloproteinases in osteosarcoma Saos-2 cells
J Orthop Res. 2007 Jul;25(7):964-71.
The actin-cytoskeleton linker protein ezrin is regulated during osteosarcoma metastasis by PKC
Oncogene. 2009; 28: 792-802. Epub Dec 2008
Publications produced with assistance from the CSBAO Journal Investigation of the insulin-like growth factor-1 signaling pathway in localized Ewing sarcoma.
Cancer 117(21): 4966–4976.
Detectable clonal mosaicism and its relationship to aging and cancer.
Nature Genetics 44(6): 651–658.
Poor Survival for Osteosarcoma of the Pelvis: A Report from the Children’s Oncology Group. .
Clinical Orthopaedics and Related Research 470(7): 2007–2013
Phase II Trial of Trastuzumab in Combination With Cytotoxic Chemotherapy for Treatment of Metastatic Osteosarcoma With Human Epidermal Growth Factor Receptor 2 Overexpression: A Report From the Children's Oncology Group.
JCO 30(20): 2545–2551.
Outcome for adolescent and young adult patients with osteosarcoma.
Cancer 118(18): 4597–4605
Publications accepted with assistance from the CSBAO Journal Chemotherapy-associated Toxicities in Overweight and Underweight Children with Osteosarcoma
PBC
Genome-wide Association Study Identifies Novel Loci Associated with Osteosarcoma
Nature Genetics
Fig 2. Successful clinically annotation for the majority of patients represented in the osteosarcoma biospecimen repository. A substantial limitation to the use of this biospecimen repository was that only 5.3% of samples from patients not enrolled on a therapeutic studies had full clinical annotation. As a result of efforts of the CSBAO, 90.8% these patient samples are now linked to clinical annotation.
Fig 3. Sample of tissue microarrays that are available to researchers. There are 52 patient sample on the array as well as 10 healthy tissues (adrenal breast and tonsil) as controls. 38 of the 52 samples have clinically annotated data available. One of the patients on the array had osteosarcoma following treatment for acute leukemia and is considered a secondary malignancy.
