Manuel Perucho

Institut de Medicina Predictiva i Personalitzada del Càncer (IMPPC)

Life & Medical Sciences

Manuel Perucho completed his PhD in Biological Sciences at the University of Madrid, Spain, in 1976 and continued as a postdoctoral at the Max-Planck-Institut, Berlin. In 1979 he moved to Cold Spring Harbor Laboratory, and in 1983 to the State University of New York (SUNY) at Stony Brook, New York. In 1988 he moved to California Institute for Biological Research (CIBR) and in 1995 to Sanford-Burnham Medical Research Institute (SBMRI), both in La Jolla, California. He was appointed Director of the Institute of Predictive and Personalized Medicine of Cancer (IMPPC) of Barcelona in 2008. His work has pioneered landmarks in the molecular basis of cancer, including the discovery of the human oncogenes in the 80's and the mutator phenotype in the 90's. Among other prizes and awards, he was recipient of a Merit Award from the National Cancer Institute for NIH grant CA 63585 and the AACR-National Foundation for Cancer Research Professorship in Basic Cancer Research in 2003.

Research interests

We aim to understand genomic and epigenomic instability as “remote” and “ultraremote” control mechanisms underlying cancer. Epigenetic alterations precede and determine the occurrence of genetic alterations: In colon tumors with microsatellite instability (MSI), age-associated DNA hypermethylation leads to a mutator phenotype when MLH1 DNA mismatch repair gene becomes epigenetically silenced. In some MSI negative tumors, DNA hypomethylation spreads during aging eventually leading to mitotic errors. Testing this “wear & tear” model yielded two instances not conforming the model (not excluding it), but revealing interesting clues on the epigenetic roots of some colon cancers: a defect increasing the demethylation observed in relatively younger patients with multiple neoplasms (synchronous and metachronous); and an exacerbated demethylation of some pericentromeric repeats especially affecting tumors with wild type TP53, linked to aberrant expression of long non-coding RNA.

Selected publications

– Buj R, Mallona I, Diez-Villanueva A, Barrera V, Mauricio D, Puig-Domingo M, Reverter JL, Matias-Guiu X, Azuara D, Ramirez JL, Alonso S, Rosell R, Capella G, Perucho M, Robledo M, Peinado MA & Jorda M 2016, ‘Quantification of Unmethylated Alu (QUAlu): a tool to assess global hypomethylation in routine clinical samples’, Oncotarget, 7, 9, 10536 – 10546.

– Kato T, Alonso S, Muto Y, Perucho M & Rikiyama T 2016, ‘Tumor size is an independent risk predictor for metachronous colorectal cancer’, Oncotarget, 7, 14, 17896 – 17904.

– Kato T, Alonso S, Noda H, Miyakura Y, Tsujinaka S, Saito M, Muto Y, Fukui T, Ichida K, Takayama Y, Watanabe F, Kakizawa N, Perucho M & Rikiyama T 2016, ‘Malignant, but not benign, intraductal papillary mucinous neoplasm preferentially associates with prior extrapancreatic malignancies’, Oncology Reports, 35, 6, 3236 – 3240.

– Paolo Fiorentino F, Tokgun E, Sole-Sanchez S, Giampaolo S, Tokgun O, Jauset T, Kohno T, Perucho MSoucek L & Yokota J 2016, ‘Growth suppression by MYC inhibition in small cell lung cancer cells with TP53 and RB1 inactivation’, Oncotarget, 7, 21, 31014 – 31028.

– Kato T, Alonso S, Muto Y, Noda H, Miyakura Y, Suzuki K, Tsujinaka S, Saito M, Perucho M & Rikiyama T 2016, ‘Clinical characteristics of synchronous colorectal cancers in Japan’, World Journal Of Surgical Oncology, 14, 272.