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Multi-dimensional scaling techniques unveiled gain1q&loss13q co-occurrence in Multiple Myeloma patients with specific genomic, transcriptional and adverse clinical features

  • Carolina Terragna,
  • Andrea Poletti,
  • Vincenza Solli,
  • Marina Martello,
  • Elena Zamagni,
  • Lucia Pantani,
  • Enrica Borsi,
  • Ilaria Vigliotta,
  • Gaia Mazzocchetti,
  • Silvia Armuzzi,
  • Barbara Taurisano,
  • Nicoletta Testoni,
  • Giulia Marzocchi,
  • Ajsi Kanapari,
  • Ignazia Pistis,
  • Paola Tacchetti,
  • Katia Mancuso,
  • Serena Rocchi,
  • Ilaria Rizzello,
  • Michele Cavo

摘要

The complexity of Multiple Myeloma (MM) is driven by several genomic aberrations, interacting with disease-related and/or -unrelated factors and conditioning patients’ clinical outcome. Patient’s prognosis is hardly predictable, as commonly employed MM risk models do not precisely partition high- from low-risk patients, preventing the reliable recognition of early relapsing/refractory patients. By a dimensionality reduction approach, here we dissect the genomic landscape of a large cohort of newly diagnosed MM patients, modelling all the possible interactions between any MM chromosomal alterations. We highlight the presence of a distinguished cluster of patients in the low-dimensionality space, with unfavorable clinical behavior, whose biology was driven by the co-occurrence of chromosomes 1q CN gain and 13 CN loss. Presence or absence of these alterations define MM patients overexpressing either CCND2 or CCND1, fostering the implementation of biology-based patients’ classification models to describe the different MM clinical behaviors.