Gene deletions and amplifications in human hepatocellular carcinomas: correlation with hepatocyte growth regulation.
Tissues from 98 human hepatocellular carcinomas (HCCs) obtained from hepatic resections were subjected to somatic copy number variation (CNV) analysis. Most of these HCCs were discovered in livers resected for orthotopic transplantation, although in a few cases, the tumors themselves were the reason for the hepatectomies. Genomic analysis revealed deletions and amplifications in several genes, and clustering analysis based on CNV revealed five clusters. The LSP1 gene had the most cases with CNV (46 deletions and 5 amplifications). High frequencies of CNV were also seen in PTPRD (21/98), GNB1L (18/98), KIAA1217 (18/98), RP1-1777G6.2 (17/98), ETS1 (11/98), RSU1 (10/98), TBC1D22A (10/98), BAHCC1 (9/98), MAML2 (9/98), RAB1B (9/98), and YIF1A (9/98). The existing literature regarding hepatocytes or other cell types has connected many of these genes to regulation of cytoskeletal architecture, signaling cascades related to growth regulation, and transcription factors directly interacting with nuclear signaling complexes. Correlations with existing literature indicate that genomic lesions associated with HCC at the level of resolution of CNV occur on many genes associated directly or indirectly with signaling pathways operating in liver regeneration and hepatocyte growth regulation.
Department of Pathology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15241, USA.
Michael A
MA
Nalesnik
George
G
Tseng
Ying
Y
Ding
Guo-Sheng
GS
Xiang
Zhong-liang
ZL
Zheng
YanPing
Y
Yu
James W
JW
Marsh
George K
GK
Michalopoulos
Jian-Hua
JH
Luo
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002455:Cell Division / Q000235:genetics; D002874:Chromosome Mapping / Q000379:methods; D016000:Cluster Analysis; D056915:DNA Copy Number Variations / Q000235:genetics; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000235:genetics; D005784:Gene Amplification; D017353:Gene Deletion; D052138:Genes, Neoplasm; D006498:Hepatectomy; D022781:Hepatocytes / Q000473:pathology*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008115:Liver Regeneration / Q000235:genetics; D008840:Microfilament Proteins / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000235:genetics
D004273:DNA, Neoplasm; C489183:LSP1 protein, human; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; C090899:PTPRD protein, human; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2