High-grade serous ovarian carcinoma (HGSOC) is a highly aggressive and intractable neoplasm, mainly because of its rapid dissemination into the abdominal cavity, a process that is favored by tumor-associated peritoneal ascites. The precise molecular alterations involved in HGSOC onset and progression remain largely unknown due to the high biological and genetic heterogeneity of this tumor. We established a set of different tumor samples (termed the As11-set) derived from a single HGSOC patient, consisting of peritoneal ascites, primary tumor cells, ovarian cancer stem cells (OCSC) and serially propagated tumor xenografts. The As11-set was subjected to an integrated RNA-seq and DNA-seq analysis which unveiled molecular alterations that marked the different types of samples. Our profiling strategy yielded a panel of signatures relevant in HGSOC and in OCSC biology. When such signatures were used to interrogate the TCGA dataset from HGSOC patients, they exhibited prognostic and predictive power. The molecular alterations also identified potential vulnerabilities associated with OCSC, which were then tested functionally in stemness-related assays. As a proof of concept, we defined PI3K signaling as a novel druggable target in OCSC.

Integrated molecular profiling of patient-derived ovarian cancer models identifies clinically relevant signatures and tumor vulnerabilities / M. Lupia, V. Melocchi, F. Bizzaro, P. Lo Riso, E. Dama, M. Baronio, A. Ranghiero, M. Barberis, L. Bernard, G. Bertalot, R. Giavazzi, G. Testa, F. Bianchi, U. Cavallaro. - In: INTERNATIONAL JOURNAL OF CANCER. - ISSN 0020-7136. - 151:2(2022 Jul 15), pp. 240-254. [10.1002/ijc.33983]

Integrated molecular profiling of patient-derived ovarian cancer models identifies clinically relevant signatures and tumor vulnerabilities

P. Lo Riso;M. Baronio;G. Testa;
2022-07-15

Abstract

High-grade serous ovarian carcinoma (HGSOC) is a highly aggressive and intractable neoplasm, mainly because of its rapid dissemination into the abdominal cavity, a process that is favored by tumor-associated peritoneal ascites. The precise molecular alterations involved in HGSOC onset and progression remain largely unknown due to the high biological and genetic heterogeneity of this tumor. We established a set of different tumor samples (termed the As11-set) derived from a single HGSOC patient, consisting of peritoneal ascites, primary tumor cells, ovarian cancer stem cells (OCSC) and serially propagated tumor xenografts. The As11-set was subjected to an integrated RNA-seq and DNA-seq analysis which unveiled molecular alterations that marked the different types of samples. Our profiling strategy yielded a panel of signatures relevant in HGSOC and in OCSC biology. When such signatures were used to interrogate the TCGA dataset from HGSOC patients, they exhibited prognostic and predictive power. The molecular alterations also identified potential vulnerabilities associated with OCSC, which were then tested functionally in stemness-related assays. As a proof of concept, we defined PI3K signaling as a novel druggable target in OCSC.
ascites; cancer stem cells; genomics; ovarian cancer; prognosis; xenograft
Settore BIO/11 - Biologia Molecolare
Settore BIO/13 - Biologia Applicata
Settore MED/04 - Patologia Generale
Settore MED/08 - Anatomia Patologica
Settore MED/40 - Ginecologia e Ostetricia
Settore MED/06 - Oncologia Medica
mar-2022
Article (author)
File in questo prodotto:
File Dimensione Formato  
Intl Journal of Cancer - 2022 - Lupia - Integrated molecular profiling of patient‐derived ovarian cancer models identifies.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 7.96 MB
Formato Adobe PDF
7.96 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/920099
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 0
  • ???jsp.display-item.citation.isi??? 0
social impact