Evaluation of Hi-C Sequencing for Detection of Gene Fusions in Hematologic and Solid Tumor Pediatric Cancer Samples
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Overview
2.2. Samples–Solid Tumors
2.3. Samples–Leukemias
2.4. Arima-HiC Sequencing
2.5. Data Analysis Workflow
3. Results
3.1. Hi-C Library Preparation and Quality Assessment
3.2. Hi-C Is Concordant with Gold-Standard Methods for Pediatric Cancer Clinical Cytogenetic Testing
3.3. Driver-Negative Leukemias–Discovery Cohort
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Sample ID | Cancer Type | Sample Source | Preservation (If Any) | Prior Cytogenetic Test Result | Hi-C Test Result |
---|---|---|---|---|---|
AML C1 | AML | PBMCs | 90% FBS/10% DMSO | CBFA2T3::GLIS2 | CBFA2T3::GLIS2 |
AML C2 | AML | Bone Marrow | None | Negative * | Negative |
AML C3 | AML | Bone Marrow | None | RUNX1::RUNX1T1 | RUNX1::RUNX1T1 |
AML C4 | AML | Bone Marrow | 90% FBS/10% DMSO | MYH11::CBFB | MYH11::CBFB |
AML C5 | AML | Bone Marrow | 90% FBS/10% DMSO | Negative ** | Negative |
AML C6 | AML | Bone Marrow | 90% FBS/10% DMSO | KMT2A::MLLT4 *** | KMT2A::MLLT4 |
AML C7 | AML | Bone Marrow | 90% FBS/10% DMSO | RUNX1::RUNX1T1 | RUNX1::RUNX1T1 |
ARMS C1 | A-RMS | Tissue | FFPE | FOXO1-r | PAX3::FOXO1 |
ARMS C2 | A-RMS | Tissue | FFPE | PAX3::FOXO1 | PAX3::FOXO1 |
ARMS C3 | A-RMS | Tissue | FFPE | PAX3::FOXO1 | PAX3::FOXO1 |
ARMS C4 | A-RMS | Tissue | FFPE | FOXO1-r | PAX7::FOXO1 |
ARMS C5 | A-RMS | Tissue | FFPE | FOX7::FOXO1 | PAX7::FOXO1 |
Sample ID | Cancer Type | Sample Source | Preservation (If Any) | Prior Dx Test Result | Hi-C Test Result | Clinical Impact |
---|---|---|---|---|---|---|
AML D1 | AML | PBMCs | 90% FBS/10% DMSO | Negative | KMT2A::MLLT10 | Dx, Px, Tx |
T-ALL D1 | T-ALL | Bone Marrow | 90% FBS/10% DMSO | Negative | SKAP2::CDK6 | Tx * |
T-ALL D2 | T-ALL | Bone Marrow | None | Negative | Negative | N/A |
B-ALL D1 | B-ALL | Bone Marrow | None | Negative | Negative | N/A |
B-ALL D2 | B-ALL | Bone Marrow | None | Negative | Negative | N/A |
B-ALL D3 | B-ALL | Bone Marrow | 90% FBS/10% DMSO | Negative | Negative | N/A |
B-ALL D4 | B-ALL | Bone Marrow | 90% FBS/10% DMSO | Negative | Negative | N/A |
B-ALL D5 | B-ALL | PBMCs | 90% FBS/10% DMSO | Negative | Negative | N/A |
B-ALL D6 | B-ALL | Bone Marrow | 90% FBS/10% DMSO | Negative | ZNF384::EP300 | Dx, Px |
B-ALL D7 | B-ALL | Bone Marrow | 90% FBS/10% DMSO | Negative | ABHD17B::PTK2B | Dx, Px ** |
B-ALL D8 | B-ALL | Bone Marrow | 90% FBS/10% DMSO | Negative | ZNF384-EP300 | Dx, Px |
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Schmitt, A.D.; Sikkink, K.; Ahmed, A.A.; Melnyk, S.; Reid, D.; Van Meter, L.; Guest, E.M.; Lansdon, L.A.; Pastinen, T.; Pushel, I.; et al. Evaluation of Hi-C Sequencing for Detection of Gene Fusions in Hematologic and Solid Tumor Pediatric Cancer Samples. Cancers 2024, 16, 2936. https://doi.org/10.3390/cancers16172936
Schmitt AD, Sikkink K, Ahmed AA, Melnyk S, Reid D, Van Meter L, Guest EM, Lansdon LA, Pastinen T, Pushel I, et al. Evaluation of Hi-C Sequencing for Detection of Gene Fusions in Hematologic and Solid Tumor Pediatric Cancer Samples. Cancers. 2024; 16(17):2936. https://doi.org/10.3390/cancers16172936
Chicago/Turabian StyleSchmitt, Anthony D., Kristin Sikkink, Atif A. Ahmed, Shadi Melnyk, Derek Reid, Logan Van Meter, Erin M. Guest, Lisa A. Lansdon, Tomi Pastinen, Irina Pushel, and et al. 2024. "Evaluation of Hi-C Sequencing for Detection of Gene Fusions in Hematologic and Solid Tumor Pediatric Cancer Samples" Cancers 16, no. 17: 2936. https://doi.org/10.3390/cancers16172936