SJPedPanel: A pan-cancer gene panel for childhood malignancies Article Swipe
Pandurang Kolekar
,
Vidya Balagopal
,
Li Dong
,
Yanling Liu
,
Scott G. Foy
,
Quang Tran
,
Heather L. Mulder
,
Anna LW Huskey
,
Emily M. Plyler
,
Zhikai Liang
,
Jingqun Ma
,
Joy Nakitandwe
,
Jiali Gu
,
Maria Namwanje
,
Jamie L. Maciaszek
,
Debbie Payne-Turner
,
Saradhi Mallampati
,
Lu Wang
,
John Easton
,
Jeffery M. Klco
,
Xiaotu Ma
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1101/2023.11.27.23299068
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1101/2023.11.27.23299068
Background Large scale genomics projects have identified driver alterations for most childhood cancers that provide reliable biomarkers for clinical diagnosis and disease monitoring using targeted sequencing. However, there is lack of a comprehensive panel that matches the list of known driver genes. Here we fill this gap by developing SJPedPanel for childhood cancers. Results SJPedPanel covers 5,275 coding exons of 357 driver genes, 297 introns frequently involved in rearrangements that generate fusion oncoproteins, commonly amplified/deleted regions (e.g., MYCN for neuroblastoma, CDKN2A and PAX5 for B-/T-ALL, and SMARCB1 for AT/RT), and 7,590 polymorphism sites for interrogating tumors with aneuploidy, such as hyperdiploid and hypodiploid B-ALL or 17q gain neuroblastoma. We used driver alterations reported from an established real-time clinical genomics cohort (n=253) to validate this gene panel. Among the 485 pathogenic variants reported, our panel covered 417 variants (86%). For 90 rearrangements responsible for oncogenic fusions, our panel covered 74 events (82%). We re-sequenced 113 previously characterized clinical specimens at an average depth of 2,500X using SJPedPanel and recovered 354 (91%) of the 389 reported pathogenic variants. We then investigated the power of this panel in detecting mutations from specimens with low tumor purity (as low as 0.1%) using cell line-based dilution experiments and discovered that this gene panel enabled us to detect ∼80% variants with allele fraction of 0.2%, while the detection rate decreases to ∼50% when the allele fraction is 0.1%. We finally demonstrate its utility in disease monitoring on clinical specimens collected from AML patients in morphologic remission. Conclusions SJPedPanel enables the detection of clinically relevant genetic alterations including rearrangements responsible for subtype-defining fusions for childhood cancers by targeted sequencing of ∼0.15% of human genome. It will enhance the analysis of specimens with low tumor burdens for cancer monitoring and early detection.
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- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2023.11.27.23299068
- https://www.medrxiv.org/content/medrxiv/early/2023/11/28/2023.11.27.23299068.full.pdf
- OA Status
- green
- References
- 86
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4389080825
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Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4389080825Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2023.11.27.23299068Digital Object Identifier
- Title
-
SJPedPanel: A pan-cancer gene panel for childhood malignanciesWork title
- Type
-
preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-11-28Full publication date if available
- Authors
-
Pandurang Kolekar, Vidya Balagopal, Li Dong, Yanling Liu, Scott G. Foy, Quang Tran, Heather L. Mulder, Anna LW Huskey, Emily M. Plyler, Zhikai Liang, Jingqun Ma, Joy Nakitandwe, Jiali Gu, Maria Namwanje, Jamie L. Maciaszek, Debbie Payne-Turner, Saradhi Mallampati, Lu Wang, John Easton, Jeffery M. Klco, Xiaotu MaList of authors in order
- Landing page
-
https://doi.org/10.1101/2023.11.27.23299068Publisher landing page
- PDF URL
-
https://www.medrxiv.org/content/medrxiv/early/2023/11/28/2023.11.27.23299068.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.medrxiv.org/content/medrxiv/early/2023/11/28/2023.11.27.23299068.full.pdfDirect OA link when available
- Concepts
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Childhood cancer, Cancer, Gene, Oncology, Medicine, Cancer research, Genetics, Internal medicine, BiologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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86Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.417 | 136 |
| abstract_inverted_index.485 | 129 |
| abstract_inverted_index.AML | 246 |
| abstract_inverted_index.For | 139 |
| abstract_inverted_index.and | 21, 82, 86, 90, 102, 167, 203, 292 |
| abstract_inverted_index.for | 10, 18, 51, 79, 84, 88, 94, 143, 264, 267, 289 |
| abstract_inverted_index.gap | 47 |
| abstract_inverted_index.its | 236 |
| abstract_inverted_index.low | 191, 195, 286 |
| abstract_inverted_index.our | 133, 146 |
| abstract_inverted_index.the | 37, 128, 172, 180, 221, 228, 254, 281 |
| abstract_inverted_index.Here | 43 |
| abstract_inverted_index.MYCN | 78 |
| abstract_inverted_index.PAX5 | 83 |
| abstract_inverted_index.cell | 199 |
| abstract_inverted_index.fill | 45 |
| abstract_inverted_index.from | 114, 188, 245 |
| abstract_inverted_index.gain | 107 |
| abstract_inverted_index.gene | 125, 207 |
| abstract_inverted_index.have | 6 |
| abstract_inverted_index.lack | 30 |
| abstract_inverted_index.list | 38 |
| abstract_inverted_index.most | 11 |
| abstract_inverted_index.rate | 223 |
| abstract_inverted_index.such | 99 |
| abstract_inverted_index.that | 14, 35, 70, 205 |
| abstract_inverted_index.then | 178 |
| abstract_inverted_index.this | 46, 124, 183, 206 |
| abstract_inverted_index.used | 110 |
| abstract_inverted_index.when | 227 |
| abstract_inverted_index.will | 279 |
| abstract_inverted_index.with | 97, 190, 215, 285 |
| abstract_inverted_index.(91%) | 170 |
| abstract_inverted_index.0.1%) | 197 |
| abstract_inverted_index.0.1%. | 232 |
| abstract_inverted_index.0.2%, | 219 |
| abstract_inverted_index.5,275 | 57 |
| abstract_inverted_index.7,590 | 91 |
| abstract_inverted_index.Among | 127 |
| abstract_inverted_index.B-ALL | 104 |
| abstract_inverted_index.Large | 2 |
| abstract_inverted_index.depth | 162 |
| abstract_inverted_index.early | 293 |
| abstract_inverted_index.exons | 59 |
| abstract_inverted_index.human | 276 |
| abstract_inverted_index.known | 40 |
| abstract_inverted_index.panel | 34, 134, 147, 184, 208 |
| abstract_inverted_index.power | 181 |
| abstract_inverted_index.scale | 3 |
| abstract_inverted_index.sites | 93 |
| abstract_inverted_index.there | 28 |
| abstract_inverted_index.tumor | 192, 287 |
| abstract_inverted_index.using | 24, 165, 198 |
| abstract_inverted_index.while | 220 |
| abstract_inverted_index.(82%). | 151 |
| abstract_inverted_index.(86%). | 138 |
| abstract_inverted_index.(e.g., | 77 |
| abstract_inverted_index.2,500X | 164 |
| abstract_inverted_index.CDKN2A | 81 |
| abstract_inverted_index.allele | 216, 229 |
| abstract_inverted_index.cancer | 290 |
| abstract_inverted_index.coding | 58 |
| abstract_inverted_index.cohort | 120 |
| abstract_inverted_index.covers | 56 |
| abstract_inverted_index.detect | 212 |
| abstract_inverted_index.driver | 8, 41, 62, 111 |
| abstract_inverted_index.events | 150 |
| abstract_inverted_index.fusion | 72 |
| abstract_inverted_index.genes, | 63 |
| abstract_inverted_index.genes. | 42 |
| abstract_inverted_index.panel. | 126 |
| abstract_inverted_index.purity | 193 |
| abstract_inverted_index.tumors | 96 |
| abstract_inverted_index.∼50% | 226 |
| abstract_inverted_index.∼80% | 213 |
| abstract_inverted_index.(n=253) | 121 |
| abstract_inverted_index.AT/RT), | 89 |
| abstract_inverted_index.Results | 54 |
| abstract_inverted_index.SMARCB1 | 87 |
| abstract_inverted_index.average | 161 |
| abstract_inverted_index.burdens | 288 |
| abstract_inverted_index.cancers | 13, 269 |
| abstract_inverted_index.covered | 135, 148 |
| abstract_inverted_index.disease | 22, 239 |
| abstract_inverted_index.enabled | 209 |
| abstract_inverted_index.enables | 253 |
| abstract_inverted_index.enhance | 280 |
| abstract_inverted_index.finally | 234 |
| abstract_inverted_index.fusions | 266 |
| abstract_inverted_index.genetic | 259 |
| abstract_inverted_index.genome. | 277 |
| abstract_inverted_index.introns | 65 |
| abstract_inverted_index.matches | 36 |
| abstract_inverted_index.provide | 15 |
| abstract_inverted_index.regions | 76 |
| abstract_inverted_index.utility | 237 |
| abstract_inverted_index.Abstract | 0 |
| abstract_inverted_index.However, | 27 |
| abstract_inverted_index.analysis | 282 |
| abstract_inverted_index.cancers. | 53 |
| abstract_inverted_index.clinical | 19, 118, 157, 242 |
| abstract_inverted_index.commonly | 74 |
| abstract_inverted_index.dilution | 201 |
| abstract_inverted_index.fraction | 217, 230 |
| abstract_inverted_index.fusions, | 145 |
| abstract_inverted_index.generate | 71 |
| abstract_inverted_index.genomics | 4, 119 |
| abstract_inverted_index.involved | 67 |
| abstract_inverted_index.patients | 247 |
| abstract_inverted_index.projects | 5 |
| abstract_inverted_index.relevant | 258 |
| abstract_inverted_index.reliable | 16 |
| abstract_inverted_index.reported | 113, 174 |
| abstract_inverted_index.targeted | 25, 271 |
| abstract_inverted_index.validate | 123 |
| abstract_inverted_index.variants | 131, 137, 214 |
| abstract_inverted_index.∼0.15% | 274 |
| abstract_inverted_index.B-/T-ALL, | 85 |
| abstract_inverted_index.childhood | 12, 52, 268 |
| abstract_inverted_index.collected | 244 |
| abstract_inverted_index.decreases | 224 |
| abstract_inverted_index.detecting | 186 |
| abstract_inverted_index.detection | 222, 255 |
| abstract_inverted_index.diagnosis | 20 |
| abstract_inverted_index.including | 261 |
| abstract_inverted_index.mutations | 187 |
| abstract_inverted_index.oncogenic | 144 |
| abstract_inverted_index.real-time | 117 |
| abstract_inverted_index.recovered | 168 |
| abstract_inverted_index.reported, | 132 |
| abstract_inverted_index.specimens | 158, 189, 243, 284 |
| abstract_inverted_index.variants. | 176 |
| abstract_inverted_index.Background | 1 |
| abstract_inverted_index.SJPedPanel | 50, 55, 166, 252 |
| abstract_inverted_index.biomarkers | 17 |
| abstract_inverted_index.clinically | 257 |
| abstract_inverted_index.detection. | 294 |
| abstract_inverted_index.developing | 49 |
| abstract_inverted_index.discovered | 204 |
| abstract_inverted_index.frequently | 66 |
| abstract_inverted_index.identified | 7 |
| abstract_inverted_index.line-based | 200 |
| abstract_inverted_index.monitoring | 23, 240, 291 |
| abstract_inverted_index.pathogenic | 130, 175 |
| abstract_inverted_index.previously | 155 |
| abstract_inverted_index.remission. | 250 |
| abstract_inverted_index.sequencing | 272 |
| abstract_inverted_index.Conclusions | 251 |
| abstract_inverted_index.alterations | 9, 112, 260 |
| abstract_inverted_index.aneuploidy, | 98 |
| abstract_inverted_index.demonstrate | 235 |
| abstract_inverted_index.established | 116 |
| abstract_inverted_index.experiments | 202 |
| abstract_inverted_index.hypodiploid | 103 |
| abstract_inverted_index.morphologic | 249 |
| abstract_inverted_index.responsible | 142, 263 |
| abstract_inverted_index.sequencing. | 26 |
| abstract_inverted_index.hyperdiploid | 101 |
| abstract_inverted_index.investigated | 179 |
| abstract_inverted_index.polymorphism | 92 |
| abstract_inverted_index.re-sequenced | 153 |
| abstract_inverted_index.characterized | 156 |
| abstract_inverted_index.comprehensive | 33 |
| abstract_inverted_index.interrogating | 95 |
| abstract_inverted_index.oncoproteins, | 73 |
| abstract_inverted_index.neuroblastoma, | 80 |
| abstract_inverted_index.neuroblastoma. | 108 |
| abstract_inverted_index.rearrangements | 69, 141, 262 |
| abstract_inverted_index.subtype-defining | 265 |
| abstract_inverted_index.amplified/deleted | 75 |
| cited_by_percentile_year | |
| corresponding_author_ids | https://openalex.org/A5102828616, https://openalex.org/A5031896350, https://openalex.org/A5025610733 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 21 |
| corresponding_institution_ids | https://openalex.org/I1313298211 |
| citation_normalized_percentile.value | 0.30953391 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |