Integrative multi-region molecular profiling of primary prostate cancer in men with synchronous lymph node metastasis

Udit Singhal (), Srinivas Nallandhighal, Jeffrey J. Tosoian, Kevin Hu, Trinh M. Pham, Judith Stangl-Kremser, Chia-Jen Liu, Razeen Karim, Komal R. Plouffe, Todd M. Morgan, Marcin Cieslik, Roberta Lucianò, Shahrokh F. Shariat, Nadia Finocchio, Lucia Dambrosio, Claudio Doglioni, Arul M. Chinnaiyan, Scott A. Tomlins, Alberto Briganti, Ganesh S. Palapattu, Aaron M. Udager () and Simpa S. Salami ()
Additional contact information
Udit Singhal: Michigan Medicine
Srinivas Nallandhighal: Michigan Medicine
Jeffrey J. Tosoian: Vanderbilt University
Kevin Hu: Michigan Medicine
Trinh M. Pham: Michigan Medicine
Judith Stangl-Kremser: Michigan Medicine
Chia-Jen Liu: University of Michigan
Razeen Karim: University of Michigan
Komal R. Plouffe: Michigan Medicine
Todd M. Morgan: Michigan Medicine
Marcin Cieslik: Michigan Medicine
Roberta Lucianò: Universita Vita-Salute San Raffaele
Shahrokh F. Shariat: Medical University of Vienna
Nadia Finocchio: Universita Vita-Salute San Raffaele
Lucia Dambrosio: Universita Vita-Salute San Raffaele
Claudio Doglioni: Universita Vita-Salute San Raffaele
Arul M. Chinnaiyan: Michigan Medicine
Scott A. Tomlins: Michigan Medicine
Alberto Briganti: Universita Vita-Salute San Raffaele
Ganesh S. Palapattu: Michigan Medicine
Aaron M. Udager: Michigan Medicine
Simpa S. Salami: Michigan Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-9

Abstract: Abstract Localized prostate cancer is frequently composed of multiple spatially distinct tumors with significant inter- and intra-tumoral molecular heterogeneity. This genomic diversity gives rise to many competing clones that may drive the biological trajectory of the disease. Previous large-scale sequencing efforts have focused on the evolutionary process in metastatic prostate cancer, revealing a potential clonal progression to castration resistance. However, the clonal origin of synchronous lymph node (LN) metastases in primary disease is still unknown. Here, we perform multi-region, targeted next generation sequencing and construct phylogenetic trees in men with prostate cancer with synchronous LN metastasis to better define the pathologic and molecular features of primary disease most likely to spread to the LNs. Collectively, we demonstrate that a combination of histopathologic and molecular factors, including tumor grade, presence of extra-prostatic extension, cellular morphology, and oncogenic genomic alterations are associated with synchronous LN metastasis.

Date: 2024
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DOI: 10.1038/s41467-024-48629-y

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