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The Angiosarcoma Project: enabling genomic and clinical discoveries in a rare cancer through patient-partnered research
- Source :
- Nature Medicine. 26:181-187
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- Despite rare cancers accounting for 25% of adult tumors1, they are difficult to study due to the low disease incidence and geographically dispersed patient populations, which has resulted in significant unmet clinical needs for patients with rare cancers. We assessed whether a patient-partnered research approach using online engagement can overcome these challenges, focusing on angiosarcoma, a sarcoma with an annual incidence of 300 cases in the United States. Here we describe the development of the Angiosarcoma Project (ASCproject), an initiative enabling US and Canadian patients to remotely share their clinical information and biospecimens for research. The project generates and publicly releases clinically annotated genomic data on tumor and germline specimens on an ongoing basis. Over 18 months, 338 patients registered for the ASCproject, which comprises a large proportion of all patients with angiosarcoma. Whole-exome sequencing (WES) of 47 tumors revealed recurrently mutated genes that included KDR, TP53, and PIK3CA. PIK3CA-activating mutations were observed predominantly in primary breast angiosarcoma, which suggested a therapeutic rationale. Angiosarcoma of the head, neck, face and scalp (HNFS) was associated with a high tumor mutation burden (TMB) and a dominant ultraviolet damage mutational signature, which suggested that for the subset of patients with angiosarcoma of HNFS, ultraviolet damage may be a causative factor and that immune checkpoint inhibition may be beneficial. Medical record review revealed that two patients with HNFS angiosarcoma had received off-label therapeutic use of antibody to the programmed death-1 protein (anti-PD-1) and had experienced exceptional responses, which highlights immune checkpoint inhibition as a therapeutic avenue for HNFS angiosarcoma. This patient-partnered approach has catalyzed an opportunity to discover the etiology and potential therapies for patients with angiosarcoma. Collectively, this proof-of-concept study demonstrates that empowering patients to directly participate in research can overcome barriers in rare diseases and can enable discoveries. A framework of patient-partnered research allows patients with angiosarcoma to share their samples and clinical records securely to accelerate molecular characterization of tumors and identification of therapeutic approaches.
- Subjects :
- 0301 basic medicine
Oncology
medicine.medical_specialty
Genomic data
Germline
General Biochemistry, Genetics and Molecular Biology
Annual incidence
03 medical and health sciences
0302 clinical medicine
Internal medicine
medicine
Angiosarcoma
neoplasms
Exome sequencing
business.industry
Incidence (epidemiology)
Medical record
General Medicine
medicine.disease
Rare cancer
Immune checkpoint
030104 developmental biology
030220 oncology & carcinogenesis
Etiology
Sarcoma
business
Subjects
Details
- ISSN :
- 1546170X and 10788956
- Volume :
- 26
- Database :
- OpenAIRE
- Journal :
- Nature Medicine
- Accession number :
- edsair.doi.dedup.....7baed62192fba289074ab7402dbc91b0