Not Missing the Notch: Detection Challenges of Juxtamembrane NOTCH1 Variant Detection in T‐Cell Acute Lymphoblastic Leukemia
Francisco Beas, Stephan Hutter, Ferran Balbastre‐Úbeda, Sandra Novoa‐Jáuregui, Maria Gabarrós‐Subirà, Eulalia Genescà, Petri Pölönen, Torsten Haferlach, Andrés Jerez · 2026
Read Not Missing the Notch: Detection Challenges of Juxtamembrane NOTCH1 Variant Detection in T‐Cell Acute Lymphoblastic Leukemia by Francisco Beas, Stephan Hutter, Ferran Balbastre‐Úbeda, Sandra Novoa‐Jáuregui, Maria Gabarrós‐Subirà, Eulalia Genescà, Petri Pölönen, Torsten Haferlach, Andrés Jerez (2026) in the Tower of Babel, a free online library of public-domain works preserved in clean, searchable text. No sign-up. The full text is served as a plain-text file at a predictable URL, where text is present: https://antarctic-labs.com/tower-of-babel/pmc-13399816.txt.
Description
Beas and colleagues warn, in 2026, that a class of leukemia-driving NOTCH1 mutations is being missed by routine genetic testing. In T-cell acute lymphoblastic leukemia, juxtamembrane internal tandem duplications in NOTCH1 activate the gene. They carry favorable prognostic meaning when RAS and PTEN are normal, but their size and sequence make them hard for short-read sequencing pipelines to call. An index case whose variant was detected discordantly by software prompted a systematic check.
In that patient, the caller VarDict found a 51-base-pair duplication that VarScan2 missed, confirmed by Sanger sequencing. Reanalyzing seven confirmed cases, Mutect2 and VarDict detected every duplication, 100 percent, Pindel caught six of seven at 85.7 percent, and VarScan2 found only three, 42.8 percent of the set. Haplotype-based callers that use soft-clipped and split reads succeeded where pileup-based callers discarded evidence. The authors urge combining calling strategies for this variant class.
Catalog record
| CREATOR | Francisco Beas, Stephan Hutter, Ferran Balbastre‐Úbeda, Sandra Novoa‐Jáuregui, Maria Gabarrós‐Subirà, Eulalia Genescà, Petri Pölönen, Torsten Haferlach, Andrés Jerez |
|---|---|
| YEAR | 2026 |
| COLLECTION | PAPERS |
| FORMAT | TXT |
| FILE SIZE | 14 KB |
| VERSION | 1.0 |
| LICENSE | CC BY 4.0 |
| RIGHTS | CC BY |
| SOURCE | Europe PMC |