Forskningsoutput per år
Forskningsoutput per år
Johan Staaf, Dominik Glodzik, Ana Bosch, Johan Vallon-Christersson, Christel Reuterswärd, Jari Häkkinen, Andrea Degasperi, Tauanne Dias Amarante, Lao H Saal, Cecilia Hegardt, Hilary Stobart, Anna Ehinger, Christer Larsson, Lisa Rydén, Niklas Loman, Martin Malmberg, Anders Kvist, Hans Ehrencrona, Helen R Davies, Åke Borg
Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift › Peer review
Whole-genome sequencing (WGS) brings comprehensive insights to cancer genome interpretation. To explore the clinical value of WGS, we sequenced 254 triple-negative breast cancers (TNBCs) for which associated treatment and outcome data were collected between 2010 and 2015 via the population-based Sweden Cancerome Analysis Network-Breast (SCAN-B) project (ClinicalTrials.gov ID:NCT02306096). Applying the HRDetect mutational-signature-based algorithm to classify tumors, 59% were predicted to have homologous-recombination-repair deficiency (HRDetect-high): 67% explained by germline/somatic mutations of BRCA1/BRCA2, BRCA1 promoter hypermethylation, RAD51C hypermethylation or biallelic loss of PALB2. A novel mechanism of BRCA1 abrogation was discovered via germline SINE-VNTR-Alu retrotransposition. HRDetect provided independent prognostic information, with HRDetect-high patients having better outcome on adjuvant chemotherapy for invasive disease-free survival (hazard ratio (HR) = 0.42; 95% confidence interval (CI) = 0.2-0.87) and distant relapse-free interval (HR = 0.31, CI = 0.13-0.76) compared to HRDetect-low, regardless of whether a genetic/epigenetic cause was identified. HRDetect-intermediate, some possessing potentially targetable biological abnormalities, had the poorest outcomes. HRDetect-low cancers also had inadequate outcomes: ~4.7% were mismatch-repair-deficient (another targetable defect, not typically sought) and they were enriched for (but not restricted to) PIK3CA/AKT1 pathway abnormalities. New treatment options need to be considered for now-discernible HRDetect-intermediate and HRDetect-low categories. This population-based study advocates for WGS of TNBC to better inform trial stratification and improve clinical decision-making.
Originalspråk | engelska |
---|---|
Sidor (från-till) | 1526–1533 |
Tidskrift | Nature Medicine |
Volym | 25 |
DOI | |
Status | Published - 2019 |
Forskningsoutput: Tidskriftsbidrag › Publicerat konferensabstract
Staaf, J. (Forskare), Karlsson, A. K. (Forskare), Aine, M. (Forskare) & Liljedahl, H. (Forskare)
2019/07/01 → 2025/10/01
Projekt: Forskning
Borg, Å. (PI), Ehinger, A. (PI), Hegardt, C. (PI), Larsson, C. (PI), Loman, N. (PI), Malmberg, M. (PI), Ryden, L. (PI) & Saal, L. (PI)
Fru Berta Kamprads stiftelse för utforskning och bekämpning av cancersjukdomar
2009/06/01 → …
Projekt: Nätverk
Ehinger, A. (medverkande)
Aktivitet: Konsultverksamhet, expertuppdrag och medlemskap › Medlem i styrelse/kommitté/råd etc