Identifying the Genomic Basis of Organ-Specific Metastasis
Although most cancer deaths are due to metastatic disease, we are still unable to predict if, when, and where an early-stage tumor will metastasize. We aim to address this question by analyzing genomic data for 10,000 patients with metastatic cancer that have undergone targeted sequencing at Memorial Sloan Kettering Cancer Center. We will curate detailed clinical annotations including timing and multiple sites of metastasis per patient, as well as response to treatment. Our final dataset will be made publicly available. We will investigate associations between genomic profiles and metastatic patterns. We will also build predictive models that assess the risk of metastatic spread at target-organ resolution and can be used to improve patient care and clinical practice.
Progress report (January 2020):
Since we started our project in December 2017, we have curated a dataset that combines genomic and clinical information for more than 30,000 cancer patients (triplicating our original target of 10,000 cases). For all of these, we have cataloged the whole set of organs affected by metastatic disease throughout the entire clinical history of each patient. The result is the first pan-cancer atlas of human metastasis that integrates histopathological and genomic information. Our data analysis results highlight associations between metastatic potential and chromosomal instability, as well as somatic alterations that are associated with organotropisms in specific cancer types.
Yearly updates of our research were presented as submitted abstracts selected for short oral talks at the annual AACR meetings in 2018 and 2019:
- Genomic characterization of organ-specific metastasis from prospective clinical sequencing of 20,000 cancer patients
- A molecular and histopathologic map of cancer metastasis
Our research has also been highlighted in the Memorial Sloan-Kettering blog:
The following manuscripts have been published thanks to the support from the BPF ICI program since the beginning of our grant:
- EGFR and MET Amplifications Determine Response to HER2 Inhibition in ERBB2-Amplified Esophagogastric Cancer (Cancer Discovery)
- EGFR mutation subtypes and response to immune checkpoint blockade treatment in non-small-cell lung cancer (Annals of Oncology)
- Genomic stratification beyond Ras/B‐Raf in colorectal liver metastasis patients treated with hepatic arterial infusion (Cancer Medicine)
Several additional manuscripts have already been submitted or are currently under preparation, and will be added to this list during the next few months.
A final manuscript to recapitulate the whole set of findings from our project and to accompany the public release of our data set is also under preparation for publication in 2020.