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© Jacob SEELER & Anne DEJEAN, Institut Pasteur
Immunostaining of PML nuclear bodies involved in acute promyelocytic leukemia
Publication : PloS one

A peculiar mutation spectrum emerging from young peruvian patients with hepatocellular carcinoma

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in PloS one - 11 Dec 2014

Marchio A, Bertani S, Rojas Rojas T, Doimi F, Terris B, Deharo E, Dejean A, Ruiz E, Pineau P

Link to Pubmed [PMID] – 25502816

PLoS ONE 2014;9(12):e114912

Hepatocellular carcinoma usually afflicts individuals in their later years following longstanding liver disease. In Peru, hepatocellular carcinoma exists in a unique clinical presentation, which affects patients around age 25 with a normal, healthy liver. In order to deepen our understanding of the molecular processes ongoing in Peruvian liver tumors, mutation spectrum analysis was carried out on hepatocellular carcinomas from 80 Peruvian patients. Sequencing analysis focused on nine genes typically altered during liver carcinogenesis, i.e. ARID2, AXIN1, BRAF, CTNNB1, NFE2L2, H/K/N-RAS, and TP53. We also assessed the transcription level of factors involved in the control of the alpha-fetoprotein expression and the Hippo signaling pathway that controls contact inhibition in metazoans. The mutation spectrum of Peruvian patients was unique with a major class of alterations represented by Insertions/Deletions. There were no changes at hepatocellular carcinoma-associated mutation hotspots in more than half of the specimens analyzed. Furthermore, our findings support the theory of a consistent collapse in the Hippo axis, as well as an expression of the stemness factor NANOG in high alpha-fetoprotein-expressing hepatocellular carcinomas. These results confirm the specificity of Peruvian hepatocellular carcinoma at the molecular genetic level. The present study emphasizes the necessity to widen cancer research to include historically neglected patients from South America, and more broadly the Global South, where cancer genetics and tumor presentation are divergent from canonical neoplasms.

http://www.ncbi.nlm.nih.gov/pubmed/25502816