Very Rare Cancer Consortium

Very Rare Cancer Consortium (VRCC): A New York Genome Center Multi-Institutional Initiative to Investigate the Molecular Drivers of Rare Disease.

Soren Germer1, Shauna Houlihan2, Theresa MacDonald2, Marie Normile2, Nicolas Robine1, Brian Robinson2, Neerav Shukla3
and Matija Snuderl4
Representing the Genome Center Cancer Group at the New York Genome Center

Co-chairs: Harold Varmus1,2 and Olivier Elemento1,2

New York Genome Center; Weill Cornell Medicine, 3 Memorial Sloan Kettering Cancer; 4 NYU Langone Medical Center


As less than one in one million people are diagnosed with very rare tumors, individual medical centers see too few patients to investigate the driving causes of the disease. As a result, most of these diseases are poorly studied and novel treatments have not been devised or tested.

The Very Rare Cancer Consortium (VRCC) aims to leverage the combined expertise from multiple institutions across New York City to advance efforts to improve research for very rare cancers. Through a network of 17 member institutions, this project will help to collect samples of very rare cancers in sufficient numbers to provide answers to important scientific questions, build research cohorts, and reduce the toll taken by understudied diseases.


While tremendous progress has been made in curing many common cancers, treatment options still remain especially limited for those diagnosed with very rare cancers. Recent advances in genomic sequencing technologies have revolutionized our understanding of tumor biology and impacted the prevention, risk assessment, early detection, diagnosis, and treatment of disease. As the first institution in New York State to receive Department of Health approval to offer a comprehensive whole genome and transcriptome oncology clinical test, the New York Genome Center (NYGC) is uniquely positioned to investigate the molecular drivers of very rare cancer types.

The Very Rare Cancer Consortium is a unified group of world-renowned clinicians and researchers across NYC collectively seeking to pinpoint the genetic cause for rare diseases. The New York Genome Center has an established framework, including: a network of clinicians, a city-wide infrastructure for sample collection, and an institutional review board (IRB) approved protocol to guarantee patient protection.


The Very Rare Cancer Consortium (VRCC) will conduct genomic analyses on very rare cancer cohorts for retrospective and prospective cases, potentially producing insights to inform treatments for patients. The goal is ultimately to identify novel treatments or new indicators for already approved therapies.

The purpose of the Very Rare Cancer Consortium are as follows:

  • Build NYC-wide cohorts of very rare cancer genomic profiles and associated scientific, clinical and patient communities to advance research
  • Provide prospective clinical insight via genomic sequencing and molecular tumor boards to improve patient care for individuals with poorly characterized tumors
  • Promote direct engagement of very rare cancer patients and post-treatment cancer survivors as participants in cancer research
  • Facilitate research on very rare cancers by developing tests to better understand molecular drivers; sharing information in well-designed databases; and by building collaborations with investigators studying rare cancers elsewhere in the US and throughout the world.

A Phased Approach

Phase I of the project aims to collect and sequence at least 20 tumors from all partnering institutions over the course of one year.  This initial phase will include sample collection, central pathology review, and the whole genome profile and analysis of samples. The Genome Center Cancer Group (GCCG) has identified the following 12 tumor types, as a sufficient number of stored samples were already identified throughout several NYC institutions, including Weill Cornell Medicine, Memorial Sloan Kettering, NYU Langone, and Columbia University Irving Medical Center.

The tumor types for Phase I include:

In Phase 2, the NYGC will partner with institutions both nationally and internationally to acquire more samples, expanding the number of cases per tumor type to at least 50. Additional profiling methods will be added to increase the number of cases sequenced per month and to create a deeper engagement with the patient advocacy community. Phase 2 will expand aims of Phase I with the continuance of tissue sample acquisition and processing; next generation sequencing; building a genomic database to distinguish patterns in very rare cancers.

Tissue Sample Acquisition and Processing: The consortium will collect tissue samples from academic centers across NYC through an established process and store the samples in a CLIA certified lab for central pathology review at the NYGC.  Clinical tests at the NYGC have been validated for fresh, frozen and FFPE (formalin fixed paraffin embedded) specimens.

Next Generation Sequencing: Whole Genome and Transcriptome Sequencing (WGTS) for oncology is a complex genetic test developed by NYGC scientists that involves sequencing the genome of the tumor, the matched normal (unaffected) specimen, and the transcriptome of the tumor specimen. Unlike gene panels or whole exome sequencing, this new test includes sequencing the coding and non-coding regions of the genome. WGTS doesn’t rely on enriching the protein-coding part of the genome or make any assumptions about the most relevant genes. It probes the transcriptome of the tumor, revealing an unbiased and more complete depiction of the patient’s cancer from a genomic and molecular perspective. The ultimate advantage of WGTS is that it can lead to more comprehensive disease diagnosis and personalized treatment decisions than tests that sequence only the coding region. 

Genomic Database: Findings from next generation sequencing tests will be stored these in a centralized database, helping to make patterns more distinct. This hub will serve as a starting point for researchers across NYC developing hypotheses. We hope that it will grow to be a global resource for understanding the genomic profiles, and provide insights to drive new therapeutic discoveries for very rare cancers.