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Therapeutic Implication of Genomic Landscape of Adult Metastatic Sarcoma.
Feng, Xiaolan; Pleasance, Erin; Zhao, Eric Y; Ng, Tony; Grewal, Jasleen K; Mohammad, Nissreen; Taylor, Sara K; Simmons, Christine; Srikanthan, Amirrtha; Rassekh, S Rod; Deyell, Rebecca; Rauw, Jennifer; Knowling, Meg; Khoo, Kong; Lee, Ursula; Noonan, Krista; Hart, Jason; Tonseth, R Petter; Shen, Yaoqing; Titmuss, Emma; Jones, Martin; Bonakdar, Melika; Reisle, Caralyn; Taylor, Greg A; Chan, Simon; Mungall, Karen; Chuah, Eric; Zhao, Yongjun; Mungall, Andrew; Moore, Richard; Lim, Howard; Renouf, Daniel J; Gelmon, Karen; Yip, Stephen; Jones, Steven J M; Marra, Marco; Laskin, Janessa.
Afiliação
  • Feng X; BC Cancer, Victoria, British Columbia, Canada.
  • Pleasance E; BC Cancer, Vancouver, British Columbia, Canada.
  • Zhao EY; BC Cancer, Vancouver, British Columbia, Canada.
  • Ng T; University of British Columbia, Vancouver, British Columbia, Canada.
  • Grewal JK; BC Cancer, Vancouver, British Columbia, Canada.
  • Mohammad N; BC Cancer, Vancouver, British Columbia, Canada.
  • Taylor SK; BC Cancer-Kelowna, Kelowna, British Columbia, Canada.
  • Simmons C; BC Cancer, Vancouver, British Columbia, Canada.
  • Srikanthan A; BC Cancer, Vancouver, British Columbia, Canada.
  • Rassekh SR; BC Children's Hospital, Vancouver, British Columbia, Canada.
  • Deyell R; BC Children's Hospital, Vancouver, British Columbia, Canada.
  • Rauw J; BC Cancer, Victoria, British Columbia, Canada.
  • Knowling M; BC Cancer, Vancouver, British Columbia, Canada.
  • Khoo K; BC Cancer, Surrey, British Columbia, Canada.
  • Lee U; BC Cancer, Surrey, British Columbia, Canada.
  • Noonan K; BC Cancer, Surrey, British Columbia, Canada.
  • Hart J; BC Cancer, Victoria, British Columbia, Canada.
  • Tonseth RP; BC Cancer, Vancouver, British Columbia, Canada.
  • Shen Y; BC Cancer, Vancouver, British Columbia, Canada.
  • Titmuss E; BC Cancer, Vancouver, British Columbia, Canada.
  • Jones M; BC Cancer, Vancouver, British Columbia, Canada.
  • Bonakdar M; BC Cancer, Vancouver, British Columbia, Canada.
  • Reisle C; BC Cancer, Vancouver, British Columbia, Canada.
  • Taylor GA; BC Cancer, Vancouver, British Columbia, Canada.
  • Chan S; BC Cancer, Vancouver, British Columbia, Canada.
  • Mungall K; BC Cancer, Vancouver, British Columbia, Canada.
  • Chuah E; BC Cancer, Vancouver, British Columbia, Canada.
  • Zhao Y; BC Cancer, Vancouver, British Columbia, Canada.
  • Mungall A; BC Cancer, Vancouver, British Columbia, Canada.
  • Moore R; BC Cancer, Vancouver, British Columbia, Canada.
  • Lim H; BC Cancer, Vancouver, British Columbia, Canada.
  • Renouf DJ; BC Cancer, Vancouver, British Columbia, Canada.
  • Gelmon K; BC Cancer, Vancouver, British Columbia, Canada.
  • Yip S; University of British Columbia, Vancouver, British Columbia, Canada.
  • Jones SJM; BC Cancer, Vancouver, British Columbia, Canada.
  • Marra M; BC Cancer, Vancouver, British Columbia, Canada.
  • Laskin J; BC Cancer, Vancouver, British Columbia, Canada.
JCO Precis Oncol ; 3: 1-25, 2019 Dec.
Article em En | MEDLINE | ID: mdl-35100702
ABSTRACT

PURPOSE:

This study investigated therapeutic potential of integrated genome and transcriptome profiling of metastatic sarcoma, a rare but extremely heterogeneous group of aggressive mesenchymal malignancies with few systemic therapeutic options.

METHODS:

Forty-three adult patients with advanced or metastatic non-GI stromal tumor sarcomas of various histology subtypes who were enrolled in the Personalized OncoGenomics program at BC Cancer were included in this study. Fresh tumor tissues along with blood samples underwent whole-genome and transcriptome sequencing.

RESULTS:

The most frequent genomic alterations in this cohort are large-scale structural variation and somatic copy number variation. Outlier RNA expression as well as somatic copy number variations, structural variations, and small mutations together suggest the presence of one or more potential therapeutic targets in the majority of patients in our cohort. Point mutations or deletions in known targetable cancer genes are rare; for example, tuberous sclerosis complex 2 provides a rationale for targeting the mammalian target of rapamycin pathway, resulting in a few patients with exceptional clinical benefit from everolimus. In addition, we observed recurrent 17p11-12 amplifications, which seem to be a sarcoma-specific event. This may suggest that this region harbors an oncogene(s) that is significant for sarcoma tumorigenesis. Furthermore, some sarcoma tumors carrying a distinct mutational signature suggestive of homologous recombination deficiency seem to demonstrate sensitivity to double-strand DNA-damaging agents.

CONCLUSION:

Integrated large-scale genomic analysis may provide insights into potential therapeutic targets as well as novel biologic features of metastatic sarcomas that could fuel future experimental and clinical research and help design biomarker-driven basket clinical trials for novel therapeutic strategies.

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2019 Tipo de documento: Article