title: TERT promoter mutations and monoallelic activation of TERT in cancer.
abstract: Here we report that promoter mutations in telomerase (TERT), the most common noncoding mutations in cancer, give rise to monoallelic expression of TERT. Through deep RNA sequencing, we find that TERT activation in human cancer cell lines can occur in either mono- or biallelic manner. Without exception, hotspot TERT promoter mutations lead to the re-expression of only one allele, accounting for approximately half of the observed cases of monoallelic TERT expression. Furthermore, we show that monoallelic TERT expression is highly prevalent in certain tumor types and widespread across a broad spectrum of cancers. Taken together, these observations provide insights into the mechanisms of TERT activation and the ramifications of noncoding mutations in cancer.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.|Department of Medicine, Harvard Medical School, Boston, MA, USA.|Cancer Program, The Broad Institute of Harvard and MIT, Cambridge, MA, USA.
authors.forename: F W
authors.initials: FW
authors.lastname: Huang
authors.affiliation: Cancer Program, The Broad Institute of Harvard and MIT, Cambridge, MA, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Bielski
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.|Cancer Program, The Broad Institute of Harvard and MIT, Cambridge, MA, USA.|Department of Neurology, Harvard Medical School, Boston, MA, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Rinne
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.|Department of Medicine, Harvard Medical School, Boston, MA, USA.|Cancer Program, The Broad Institute of Harvard and MIT, Cambridge, MA, USA.
authors.forename: W C
authors.initials: WC
authors.lastname: Hahn
authors.affiliation: Oncology Disease Area, Novartis Institutes for Biomedical Research, Cambridge, MA, USA.
authors.forename: W R
authors.initials: WR
authors.lastname: Sellers
authors.affiliation: Department of Neurology, Harvard Medical School, Boston, MA, USA.
authors.forename: F
authors.initials: F
authors.lastname: Stegmeier
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.|Department of Medicine, Harvard Medical School, Boston, MA, USA.|Cancer Program, The Broad Institute of Harvard and MIT, Cambridge, MA, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Garraway
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.|Cancer Program, The Broad Institute of Harvard and MIT, Cambridge, MA, USA.|Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: G V
authors.initials: GV
authors.lastname: Kryukov