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Gellert, Pascal; Segal, Corrinne V; Gao, Qiong; López-Knowles, Elena; Martin, Lesley-Ann; Dodson, Andrew; Li, Tiandao; Miller, Christopher A; Lu, Charles; Mardis, Elaine R; Gillman, Alexa; Morden, James; Graf, Manuela; Sidhu, Kally; Evans, Abigail; Shere, Michael; Holcombe, Christopher; McIntosh, Stuart A; Bundred, Nigel; Skene, Anthony; Maxwell, William; Robertson, John; Bliss, Judith M; Smith, Ian; Dowsett, Mitch
Nature communications, 11/2016, Letnik: 7, Številka: 1Journal Article
Pre-surgical studies allow study of the relationship between mutations and response of oestrogen receptor-positive (ER+) breast cancer to aromatase inhibitors (AIs) but have been limited to small biopsies. Here in phase I of this study, we perform exome sequencing on baseline, surgical core-cuts and blood from 60 patients (40 AI treated, 20 controls). In poor responders (based on Ki67 change), we find significantly more somatic mutations than good responders. Subclones exclusive to baseline or surgical cores occur in ∼30% of tumours. In phase II, we combine targeted sequencing on another 28 treated patients with phase I. We find six genes frequently mutated: PIK3CA, TP53, CDH1, MLL3, ABCA13 and FLG with 71% concordance between paired cores. TP53 mutations are associated with poor response. We conclude that multiple biopsies are essential for confident mutational profiling of ER+ breast cancer and TP53 mutations are associated with resistance to oestrogen deprivation therapy.
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Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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