TY - JOUR
T1 - Multiregional genetic evolution of metastatic uveal melanoma
AU - Rodriguez, Daniel A.
AU - Yang, Jessica
AU - Durante, Michael A.
AU - Shoushtari, Alexander N.
AU - Moschos, Stergios J.
AU - Wrzeszczynski, Kazimierz O.
AU - Harbour, J. William
AU - Carvajal, Richard D.
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and leads to deadly metastases for which there is no approved treatment. Genetic events driving early tumor development are well-described, but those occurring later during metastatic progression remain poorly understood. We performed multiregional genomic sequencing on 22 tumors collected from two patients with widely metastatic UM who underwent rapid autopsy. We observed multiple seeding events from the primary tumors, metastasis-to-metastasis seeding, polyclonal seeding, and late driver variants in ATM, KRAS, and other genes previously unreported in UM. These findings reveal previously unrecognized temporal and anatomic complexity in the genetic evolution of metastatic uveal melanoma, and they highlight the distinction between early and late phases of UM genetic evolution with implications for novel therapeutic approaches.
AB - Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and leads to deadly metastases for which there is no approved treatment. Genetic events driving early tumor development are well-described, but those occurring later during metastatic progression remain poorly understood. We performed multiregional genomic sequencing on 22 tumors collected from two patients with widely metastatic UM who underwent rapid autopsy. We observed multiple seeding events from the primary tumors, metastasis-to-metastasis seeding, polyclonal seeding, and late driver variants in ATM, KRAS, and other genes previously unreported in UM. These findings reveal previously unrecognized temporal and anatomic complexity in the genetic evolution of metastatic uveal melanoma, and they highlight the distinction between early and late phases of UM genetic evolution with implications for novel therapeutic approaches.
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U2 - 10.1038/s41525-021-00233-5
DO - 10.1038/s41525-021-00233-5
M3 - Article
C2 - 34400647
AN - SCOPUS:85112713106
SN - 2056-7944
VL - 6
JO - npj Genomic Medicine
JF - npj Genomic Medicine
IS - 1
M1 - 70
ER -