ORIEN Intermember Projects: An Alliance Fostering Collaboration & Efficiency in High Impact Cancer Research

M2GEN is an oncology-focused informatics company committed to achieving research breakthroughs and promoting positive patient outcomes. We proudly share these goals with a vast and diverse network of cancer centers, biopharmaceutical companies, and scientists across the nation. Collectively, we believe we can accomplish much more through team science than we ever could as individual contributors.

Through the powerful Oncology Research Information Exchange Network® (ORIEN) Avatar Research Program, M2GEN is continually harnessing the considerable strength in numbers as we take on some of the toughest questions in oncology today. By joining forces with various cancer research stakeholders and sharing knowledge through this alliance, we are hastening the discovery, development, and delivery of precision cancer medicine.

Value-Added Data

In addition to a wide network of potential research collaborators, ORIEN members have access to Avatar, a longitudinal database that houses de-identified genomic and clinical information from patients consented to the Total Cancer Care® Protocol (TCC) across the network. Our research partners can utilize this rich, real-world data (RWD) to generate insights, or real-world evidence (RWE), about the safety and effectiveness of a cancer therapy or treatment regimen in a setting outside of a traditional, controlled clinical trial environment.

M2GEN’s efforts extend far beyond collecting data and building a cancer research database. M2GEN works closely with our sequencing partners and ORIEN members to standardize and harmonize this massive dataset. This thoroughgoing effort enables our research partners to unlock the valuable clinical and genomic knowledge within the depths of Avatar, making it easily accessible and utilized to its fullest potential.

ORIEN Intermember Projects

In keeping with our mission to pioneer and foster scientific discovery, M2GEN encourages highly targeted cancer studies through shared research initiatives between ORIEN member institutions and other extramural industry partners. ORIEN Intermember Projects provide a unique forum for scientific and clinical experts to exchange ideas on projects of mutual interest. M2GEN also facilitates scientific exchanges and spearheads high-interest, high-impact research areas through the ORIEN Research Interest Groups (RIGs), such as the immune-oncology RIG and sarcoma RIG, just to name a few. The ORIEN RIGs aim to contribute new and noval scientific knowledge to the cancer research community, for example:

The ORIEN Sarcoma RIG and M2GEN recently presented the results of an ORIEN Intermember Project entitled “Landscape of Anaplastic Lymphoma Kinase (ALK) Fusions in Soft Tissue Sarcomas (STS)” at the 2020 Annual Meeting of the Connective Tissue Oncology Society (CTOS), an international scientific forum focuses on sarcoma advancing the treatment of sarcomas through shared knowledge, experiences, ideas, and passion.

The Landscape of ALK Fusions in STS

Capitalizing on the vast and highly refined data available through ORIEN, this groundbreaking study encompassed the most in-depth evaluation of ALK fusion events in STS performed to date. The outcome was noteworthy to the CTOS for the following reason: ALK is a targetable receptor tyrosine kinase that is often activated via fusion with various genomics partners. For instance, ALK fusions are implicated in the oncogenesis of many lymphomas and solid tumors. However, in sarcomas, ALK fusions (balanced translations) and ALK transcription-induced chimeras (read-through events) are not yet well understood.

Utilizing highly accurate STAR-Fusion and Arriba algorithms, we evaluated RNA sequencing (RNA-Seq) data from 727 patients representing 69 distinct STS histologies for ALK fusions. Through Avatar, we were able to limit our analysis to high-quality putative fusion events with breakpoints greater than 400 kilobases (kb) in genomic distance. We retained any predictions that generated a high/medium confidence score from Arriba (fusion fragments per million total RNA-Seq fragments (FFPM) greater than or equal to 0.1). To estimate the statistical significance of our findings, we used Fisher’s exact test of independence.

As a result of this study, we determined that ALK fusions are rare events in sarcomas, a finding that is consistent with reports from pain-cancer analyses. In our analysis of STS, we found that ALK was fused to seven different partner genes. Specifically, we observed IGFBP5-ALK, a known fusion in inflammatory myofibroblastic tumors (IMT). Also, in myxoid liposarcomas (MLS), we recurrently observed Ino-ALK-1 (AC016907.2), a novel fusion that may be a transcription-induced chimera. In conclusion, we believe the further study of ALK activation, and potentially ALK targeting in MLS, is warranted.

STS are diverse cancers that comprise more than 100 histological and molecular subtypes. Coupled with their rarity, the diversity of STS underscores the need for collaboration in developing specific treatment protocols. ORIEN Intermember Projects like this one can expand the existing knowledge base about the complexities of STS as defined by molecular biology, a promising start that can potentially lead to the introduction of targeted therapies for distinct sarcoma subtypes.

Driving the Discoveries That Transform Cancer Care

Precision medicine—which directly results from ORIEN Intermember Projects—is shaping the future of cancer care. Serving as the operational engine of ORIEN, M2GEN has earned respect as a leader in creating and delivering bioinformatics solutions, which can help our partners predict and meet the highly unique needs of cancer patients.

Contact M2GEN today to learn more about the boundless potential of ORIEN, as well as our pivotal role in coordinating ORIEN Intermember Projects that are paving the way for tailored cancer treatment.