TLA is based on proximity ligation and yields complete sequence information across the targeted locus, including SNVs and structural variants.
Since TLA uses the physical proximity of sequences as the basis of selection and is based on the crosslinking and fragmenting of DNA, it has particular advantages in the detection of structural variation in FFPE samples.
Cergentis is currently developing TLA protocols for FFPE samples (see press release).
Complete cancer gene sequencing is highly relevant for different applications in oncology, such as:
- Detecting gene fusions with recurrent and novel fusion partners.
- Determining the gene fusion breakpoints at DNA level, which can serve as a robust and sensitive marker for ctDNA monitoring.
- Complete sequencing of tumour suppressor genes to detect all mutations including deletions and promoter/intronic events.
- Analyzing complex rearrangements, genomic events underlying CNVs and novel resistance mechanisms.
"Thank you so much. Data about the structural changes in our patient are very clear. Really powerful technology!”Alfredo Brusco Ph.D.(Department of Medical Sciences, University of Turin, Italy)
"Unknown translocation partners that drive expression of oncogenes as consequence of cryptic or previous unidentified chromosomal rearrangements were identified in T-cell leukemia patients using Targeted Locus Amplification.”Jules Meijerink Ph.D.(Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands)
"Targeted Locus Amplification enables fast identification of new chromosomal rearrangements and genomic breakpoint sequences in human T-ALL and unravelled a higher complexity of chromosomal translocations of known T-ALL oncogenes as thus far appreciated.”Pieter van Vlierberghe Ph.D.(Center for Medical Genetics, Ghent University, Belgium)
"We conclude that TLA is an effective method for the reliable detection of sequence mutations and structural variations that are relevant for disease prognosis in pediatric leukemia.”Roland Kuiper Ph.D.(Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands)
- Application notes
Meisel C et al. (2017)
DKFZ, Medical Genetic Center Munich, National Center for Tumor Diseases (NCT), TU Dresden, University Kiel
Toy W et al. (2016)
AstraZeneca, Memorial Sloan Kettering Cancer Center, University of Chicago & University of Illinois at Urbana Champaign
Ter Brugge P et al. (2016)
Bellvitge Biomedical Research Institute Barcelona, Curie Institute, ICREA, Institute of Cancer Research London, The Netherlands Cancer Institute, University of Barcelona & University Medical Center Utrecht
Macintyre G et al. (2016)
University of Cambridge & VU University Medical Center
Hastings RJ et al. (2015)
Charles University Prague, CHUV, Great Ormond St Hospital, Gustave Roussy, Hospital del Mar, Institute of Genomic Medicine, Oslo University Hospital, Ospedale di Circolo-Polo Universitario, Our Lady's Children's Hospital, Oxford University Hospitals NHS Trust, Radboud University Medical Center, St James's Hospital, University of Cagliari, University of Groningen, University Hospital Ghent, UZ Leuven, VU University Medical Center