Tissue-based genomic profiling of 300,000 tumors highlights the detection of variants with low allele fraction
Abstract Tumor tissues obtained in the clinical setting typically have low purity and display treatment-associated genetic heterogeneity, contributing to variants at low variant allele fractions (VAF). We present a pan-cancer landscape and the therapeutic impact of somatic variants detected at low V...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-06-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-025-00991-w |
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| author | Saumya D. Sisoudiya Hanna Tukachinsky Rachel B. Keller-Evans Alexa B. Schrock Richard S. P. Huang Ole Gjoerup Michael J. Pishvaian Rachna Shroff Ethan S. Sokol Lucas Dennis Garrett M. Frampton Smruthy Sivakumar |
| author_facet | Saumya D. Sisoudiya Hanna Tukachinsky Rachel B. Keller-Evans Alexa B. Schrock Richard S. P. Huang Ole Gjoerup Michael J. Pishvaian Rachna Shroff Ethan S. Sokol Lucas Dennis Garrett M. Frampton Smruthy Sivakumar |
| author_sort | Saumya D. Sisoudiya |
| collection | DOAJ |
| description | Abstract Tumor tissues obtained in the clinical setting typically have low purity and display treatment-associated genetic heterogeneity, contributing to variants at low variant allele fractions (VAF). We present a pan-cancer landscape and the therapeutic impact of somatic variants detected at low VAF (≤10%) from tumor tissues in 331,503 patients, across 78 tumor types, that received an FDA-approved comprehensive genomic profiling (CGP) test targeting ~324 genes during routine clinical care. 29% of patients had at least one variant detected at VAF ≤10% and 16% at VAF ≤5%. Among the frequently diagnosed tumors, several cases showed low VAF variants: pancreatic (37%), non-small cell lung cancer (35%), colorectal (29%) and prostate (24%). Treatment resistance-associated alterations had lower median VAF than driver alterations, although variants with VAF ≤5% comprised both driver and resistance alterations. This highlights the importance of CGP in detecting low VAF variants, to better inform clinical actionability and guide personalized treatment for patients with cancer. |
| format | Article |
| id | doaj-art-13c3694e1d8f4eb3a9edc367aad1dadb |
| institution | DOAJ |
| issn | 2397-768X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj-art-13c3694e1d8f4eb3a9edc367aad1dadb2025-08-20T03:22:46ZengNature Portfolionpj Precision Oncology2397-768X2025-06-01911910.1038/s41698-025-00991-wTissue-based genomic profiling of 300,000 tumors highlights the detection of variants with low allele fractionSaumya D. Sisoudiya0Hanna Tukachinsky1Rachel B. Keller-Evans2Alexa B. Schrock3Richard S. P. Huang4Ole Gjoerup5Michael J. Pishvaian6Rachna Shroff7Ethan S. Sokol8Lucas Dennis9Garrett M. Frampton10Smruthy Sivakumar11Foundation Medicine Inc.Foundation Medicine Inc.Foundation Medicine Inc.Foundation Medicine Inc.Foundation Medicine Inc.Foundation Medicine Inc.Johns Hopkins University School of MedicineUniversity of Arizona Cancer CenterFoundation Medicine Inc.Foundation Medicine Inc.Foundation Medicine Inc.Foundation Medicine Inc.Abstract Tumor tissues obtained in the clinical setting typically have low purity and display treatment-associated genetic heterogeneity, contributing to variants at low variant allele fractions (VAF). We present a pan-cancer landscape and the therapeutic impact of somatic variants detected at low VAF (≤10%) from tumor tissues in 331,503 patients, across 78 tumor types, that received an FDA-approved comprehensive genomic profiling (CGP) test targeting ~324 genes during routine clinical care. 29% of patients had at least one variant detected at VAF ≤10% and 16% at VAF ≤5%. Among the frequently diagnosed tumors, several cases showed low VAF variants: pancreatic (37%), non-small cell lung cancer (35%), colorectal (29%) and prostate (24%). Treatment resistance-associated alterations had lower median VAF than driver alterations, although variants with VAF ≤5% comprised both driver and resistance alterations. This highlights the importance of CGP in detecting low VAF variants, to better inform clinical actionability and guide personalized treatment for patients with cancer.https://doi.org/10.1038/s41698-025-00991-w |
| spellingShingle | Saumya D. Sisoudiya Hanna Tukachinsky Rachel B. Keller-Evans Alexa B. Schrock Richard S. P. Huang Ole Gjoerup Michael J. Pishvaian Rachna Shroff Ethan S. Sokol Lucas Dennis Garrett M. Frampton Smruthy Sivakumar Tissue-based genomic profiling of 300,000 tumors highlights the detection of variants with low allele fraction npj Precision Oncology |
| title | Tissue-based genomic profiling of 300,000 tumors highlights the detection of variants with low allele fraction |
| title_full | Tissue-based genomic profiling of 300,000 tumors highlights the detection of variants with low allele fraction |
| title_fullStr | Tissue-based genomic profiling of 300,000 tumors highlights the detection of variants with low allele fraction |
| title_full_unstemmed | Tissue-based genomic profiling of 300,000 tumors highlights the detection of variants with low allele fraction |
| title_short | Tissue-based genomic profiling of 300,000 tumors highlights the detection of variants with low allele fraction |
| title_sort | tissue based genomic profiling of 300 000 tumors highlights the detection of variants with low allele fraction |
| url | https://doi.org/10.1038/s41698-025-00991-w |
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