Comprehensive Lymphatic Anomaly Revealing and Understanding GenoMics (CLARUM)

This technology is a pair of complementary cell-based and cell-free DNA genetic panels that simultaneously detect germline and somatic variants to diagnose primary Lymphatic Anomalies (LAs) ## Unmet Need: Existing panels miss most LA genes and variants -- without knowing the genetic cause, clinicians are unable to select targeted and potentially lifesaving therapy an LA patient needs Currently, there is no comprehensive LA panel-- diagnosis of primary LAs relies on fragmented commercial and academic panels with limited gene coverage, detecting either germline or somatic variants. This forces sequential testing across incomplete panels and leaves more than two-thirds of LA patients without an identified pathogenic variant or incomplete genetic diagnosis. Patients often receive a diagnosis only after years of disease progression and most never receive an identified pathogenic variant delaying precision medicine guided therapies for a progress disease. ## The Technology: A one stop comprehensive testing solution for LA patients, designed to end the diagnostic odyssey and enable pathway-directed therapy The technology consists of two complementary next-generation sequencing panels that query a comprehensive set of genes associated with primary LAs for germline and somatic variants in a single workflow. The cell-based panel accepts blood and tissue specimens, while the cell-free DNA panel accepts lymphatic fluid and plasma, enabling diagnostic access in fetal, pediatric, and tissue-limited clinical settings where lesional biopsy is not feasible. Both panels have been developed with greater than 1000-fold sequencing coverage across all exons. Analytical validation is currently underway using patient DNA and cell-free DNA, and clinical validation is being conducted across CLARUM partnered institutions. ## Applications: * Comprehensive genetic diagnosis across LA patient lifespan * Clinical decision support for therapy selection and family counseling * Companion diagnostic for patient stratification in targeted-therapy clinical trials * Research tool for lymphatic anomaly variant and gene discovery ## Advantages: * Simultaneous germline and somatic variant detection in a single workflow * Broad gene and exome coverage among LA panels * Reduces sequential testing across incomplete panels ## Lead Inventors: [Carrie Shawber, Ph.D.](https://www.obgyn.columbia.edu/profile/carrie-shawber) [Hakon Hakonarson, M.D., Ph.D.](https://www.chop.edu/doctors/hakonarson-hakon) ## Patent Information: Hakonarson, H. et. al. Compositions and methods for the diagnosis and treatment of lymphatic system disorders. US Patent No. 11,401,553, 2022. * [Rogerson D, Alkelai A, Giordano J, Pantrangi M, Hsiao MC, Nhan-Chang CL, Motelow JE, Aggarwal V, Goldstein D, Wapner R, Shawber CJ. "Investigation into the genetics of fetal congenital lymphatic anomalies" Prenatal Diagnosis. 2023 Jun; 43(6): 703-716.](https://pubmed.ncbi.nlm.nih.gov/36959127/) * [Rogerson D, Vogel Z, Muley A, Shawber CJ. "Roles for RERE in lymphatic endothelial cell proliferation and survival, and human cystic lymphatic malformations" bioRxiv preprint. 2024 Mar.](https://www.biorxiv.org/content/10.1101/2024.03.24.586490v2) * Li D, Sheppard SE, March ME, Battig MR, Surrey LF, Srinivasan AS, Matsuoka LS, Tian L, Wang F, Seiler C, Dayneka J, Borst AJ, Matos MC, Paulissen SM, Krishnamurthy G, Nriagu B, Sikder T, Casey M, Williams L, Rangu S, O'Connor N, Thomas A, Pinto E, Hou C, Nguyen K, Pellegrino da Silva R, Chehimi SN, Kao C, Biroc L, Britt AD, Queenan M, Reid JR, Napoli JA, Low DM, Vatsky S, Treat J, Smith CL, Cahill AM, Snyder KM, Adams DM, Dori Y, Hakonarson H. Genomic profiling informs diagnoses and treatment in vascular anomalies. Nat Med. 2023 Jun;29(6):1530-1539. (https://pubmed.ncbi.nlm.nih.gov/37264205/) ## Tech Ventures Reference: * Licensing Contact: [Cynthia Lang](mailto:techtransfer@columbia.edu) This research was funded, in part, by the Advanced Research Projects Agency for Health (ARPA-H) under Agreement No. 1AY2AX000086-01. The views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the U.S. Government.