Top

Published in:

01-04-2011 | Original Article

Gene expression profiling of human hepatoblastoma using archived formalin-fixed and paraffin-embedded tissues

Authors: Eun Shin, Kyoung-Bun Lee, Soo-Young Park, Soo-Hee Kim, Han-Suk Ryu, Young-Nyun Park, Eunsil Yu, Ja-June Jang

Published in: Virchows Archiv | Issue 4/2011

Abstract

We elucidated the genetic profile of hepatoblastomas (HBLs) to identify diagnostic and prognostic markers. RNA was extracted from 32 formalin-fixed, paraffin-embedded HBLs and corresponding nonneoplastic liver (NNL) tissues, and cDNA-mediated annealing, selection, extension, and ligation (DASL) chip assays were performed. Immunohistochemistry was performed to confirm the expression of Yin Yang 1 (YY1) protein in HBL. Twenty-four genes that were associated with signal transduction, cell–cell adhesion, cell cycle regulation, and apoptosis were differentially expressed in HBL and NNL tissues. Two apoptosis-associated genes, MYCN and BIRC5, were highly upregulated in HBL. Eight genes, including YY1 and IGF1, were upregulated in HBL cases that had a poor prognosis. Thirty-eight genes, including YY1, were differentially expressed according to histologic differentiation of HBL, and the immunohistochemical expression of YY1 was correlated with poor HBL differentiation. Thus, using DASL chip assays, we report the gene expression profiles of HBL, which suggest new candidate prognostic and diagnostic genetic markers and putative therapeutic targets for HBL.

Roebuck DJ, Perilongo G (2006) Hepatoblastoma: an oncological review. Pediatr Radiol 36:183–186PubMedCrossRef

Schnater JM, Kohler SE, Lamers WH, von Schweinitz D, Aronson DC (2003) Where do we stand with hepatoblastoma? A review. Cancer 98:668–678PubMedCrossRef

Hu J, Wills M, Baker BA, Perlman EJ (2000) Comparative genomic hybridization analysis of hepatoblastomas. Genes Chromosom Cancer 27:196–201PubMedCrossRef

Weber RG, Pietsch T, von Schweinitz D, Lichter P (2000) Characterization of genomic alterations in hepatoblastomas. A role for gains on chromosomes 8q and 20 as predictors of poor outcome. Am J Pathol 157:571–578PubMedCrossRef

Curia MC, Zuckermann M, De Lellis L, Catalano T, Lattanzio R, Aceto G, Veschi S, Cama A, Otte JB, Piantelli M, Mariani-Costantini R, Cetta F, Battista P (2008) Sporadic childhood hepatoblastomas show activation of beta-catenin, mismatch repair defects and p53 mutations. Mod Pathol 21:7–14PubMedCrossRef

Jeng YM, Wu MZ, Mao TL, Chang MH, Hsu HC (2000) Somatic mutations of beta-catenin play a crucial role in the tumorigenesis of sporadic hepatoblastoma. Cancer Lett 152:45–51PubMedCrossRef

Akmal SN, Yun K, MacLay J, Higami Y, Ikeda T (1995) Insulin-like growth factor 2 and insulin-like growth factor binding protein 2 expression in hepatoblastoma. Hum Pathol 26:846–851PubMedCrossRef

Gray SG, Eriksson T, Ekstrom C, Holm S, von Schweinitz D, Kogner P, Sandstedt B, Pietsch T, Ekstrom TJ (2000) Altered expression of members of the IGF-axis in hepatoblastomas. Br J Cancer 82:1561–1567PubMedCrossRef

Golub TR, Slonim DK, Tamayo P, Huard C, Gaasenbeek M, Mesirov JP, Coller H, Loh ML, Downing JR, Caligiuri MA, Bloomfield CD, Lander ES (1999) Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 286:531–537PubMedCrossRef

10.

Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, Brown PO, Botstein D (2000) Molecular portraits of human breast tumours. Nature 406:747–752PubMedCrossRef

11.

Boyer J, Allen WL, McLean EG, Wilson PM, McCulla A, Moore S, Longley DB, Caldas C, Johnston PG (2006) Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer. Cancer Res 66:2765–2777PubMedCrossRef

12.

Dhanasekaran SM, Barrette TR, Ghosh D, Shah R, Varambally S, Kurachi K, Pienta KJ, Rubin MA, Chinnaiyan AM (2001) Delineation of prognostic biomarkers in prostate cancer. Nature 412:822–826PubMedCrossRef

13.

Nagata T, Takahashi Y, Ishii Y, Asai S, Nishida Y, Murata A, Koshinaga T, Fukuzawa M, Hamazaki M, Asami K, Ito E, Ikeda H, Takamatsu H, Koike K, Kikuta A, Kuroiwa M, Watanabe A, Kosaka Y, Fujita H, Miyake M, Mugishima H (2003) Transcriptional profiling in hepatoblastomas using high-density oligonucleotide DNA array. Cancer Genet Cytogenet 145:152–160PubMedCrossRef

14.

Luo JH, Ren B, Keryanov S, Tseng GC, Rao UN, Monga SP, Strom S, Demetris AJ, Nalesnik M, Yu YP, Ranganathan S, Michalopoulos GK (2006) Transcriptomic and genomic analysis of human hepatocellular carcinomas and hepatoblastomas. Hepatology 44:1012–1024PubMedCrossRef

15.

Yamada S, Ohira M, Horie H, Ando K, Takayasu H, Suzuki Y, Sugano S, Hirata T, Goto T, Matsunaga T, Hiyama E, Hayashi Y, Ando H, Suita S, Kaneko M, Sasaki F, Hashizume K, Ohnuma N, Nakagawara A (2004) Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas. Oncogene 23:5901–5911PubMedCrossRef

16.

Bibikova M, Talantov D, Chudin E, Yeakley JM, Chen J, Doucet D, Wickham E, Atkins D, Barker D, Chee M, Wang Y, Fan JB (2004) Quantitative gene expression profiling in formalin-fixed, paraffin-embedded tissues using universal bead arrays. Am J Pathol 165:1799–1807PubMedCrossRef

17.

Hoshida Y, Villanueva A, Kobayashi M, Peix J, Chiang DY, Camargo A, Gupta S, Moore J, Wrobel MJ, Lerner J, Reich M, Chan JA, Glickman JN, Ikeda K, Hashimoto M, Watanabe G, Daidone MG, Roayaie S, Schwartz M, Thung S, Salvesen HB, Gabriel S, Mazzaferro V, Bruix J, Friedman SL, Kumada H, Llovet JM, Golub TR (2008) Gene expression in fixed tissues and outcome in hepatocellular carcinoma. N Engl J Med 359:1995–2004PubMedCrossRef

18.

Fan JB, Yeakley JM, Bibikova M, Chudin E, Wickham E, Chen J, Doucet D, Rigault P, Zhang B, Shen R, McBride C, Li HR, Fu XD, Oliphant A, Barker DL, Chee MS (2004) A versatile assay for high-throughput gene expression profiling on universal array matrices. Genome Res 14:878–885PubMedCrossRef

19.

Fan JB, Oliphant A, Shen R, Kermani BG, Garcia F, Gunderson KL, Hansen M, Steemers F, Butler SL, Deloukas P, Galver L, Hunt S, McBride C, Bibikova M, Rubano T, Chen J, Wickham E, Doucet D, Chang W, Campbell D, Zhang B, Kruglyak S, Bentley D, Haas J, Rigault P, Zhou L, Stuelpnagel J, Chee MS (2003) Highly parallel SNP genotyping. Cold Spring Harb Symp Quant Biol 68:69–78PubMedCrossRef

20.

Schwab M (2004) MYCN in neuronal tumours. Cancer Lett 204:179–187PubMedCrossRef

21.

Mertens F, Mandahl N, Mitelman F, Heim S (1994) Cytogenetic analysis in the examination of solid tumors in children. Pediatr Hematol Oncol 11:361–377PubMedCrossRef

22.

Morgenstern DA, Anderson J (2006) MYCN deregulation as a potential target for novel therapies in rhabdomyosarcoma. Expert Rev Anticancer Ther 6:217–224PubMedCrossRef

23.

Tsuda H, Shimosato Y, Upton MP, Yokota J, Terada M, Ohira M, Sugimura T, Hirohashi S (1988) Retrospective study on amplification of N-myc and c-myc genes in pediatric solid tumors and its association with prognosis and tumor differentiation. Lab Invest 59:321–327PubMed

24.

Mares J, Polanska V, Gorgens H, Sedlacek Z, Marikova T, Bocek P, Kodet R, Schackert J, Goetz P (1998) Oncogene amplification and expression in pediatric solid tumors. Neoplasma 45:123–127PubMed

25.

Fest S, Huebener N, Bleeke M, Durmus T, Stermann A, Woehler A, Baykan B, Zenclussen AC, Michalsky E, Jaeger IS, Preissner R, Hohn O, Weixler S, Gaedicke G, Lode HN (2009) Survivin minigene DNA vaccination is effective against neuroblastoma. Int J Cancer 125:104–114PubMedCrossRef

26.

Eckerle I, Muth D, Batzler J, Henrich KO, Lutz W, Fischer M, Witt O, Schwab M, Westermann F (2009) Regulation of BIRC5 and its isoform BIRC5-2B in neuroblastoma. Cancer Lett 285:99–107PubMedCrossRef

27.

Yoshida R, Ogata T, Masawa N, Nagai T (2008) Hepatoblastoma in a Noonan syndrome patient with a PTPN11 mutation. Pediatr Blood Cancer 50:1274–1276PubMedCrossRef

28.

Adesina AM, Lopez-Terrada D, Wong KK, Gunaratne P, Nguyen Y, Pulliam J, Margolin J, Finegold MJ (2009) Gene expression profiling reveals signatures characterizing histologic subtypes of hepatoblastoma and global deregulation in cell growth and survival pathways. Hum Pathol 40:843–853PubMedCrossRef

29.

LeRoith D, Roberts CT Jr (2003) The insulin-like growth factor system and cancer. Cancer Lett 195:127–137PubMed

30.

Braconi C, Bracci R, Bearzi I, Bianchi F, Sabato S, Mandolesi A, Belvederesi L, Cascinu S, Valeri N, Cellerino R (2008) Insulin-like growth factor (IGF) 1 and 2 help to predict disease outcome in GIST patients. Ann Oncol 19:1293–1298PubMedCrossRef

31.

Gordon S, Akopyan G, Garban H, Bonavida B (2006) Transcription factor YY1: structure, function, and therapeutic implications in cancer biology. Oncogene 25:1125–1142PubMedCrossRef

Title: Gene expression profiling of human hepatoblastoma using archived formalin-fixed and paraffin-embedded tissues
Authors: Eun Shin
Kyoung-Bun Lee
Soo-Young Park
Soo-Hee Kim
Han-Suk Ryu
Young-Nyun Park
Eunsil Yu
Ja-June Jang
Publication date: 01-04-2011
Publisher: Springer-Verlag
Published in: Virchows Archiv / Issue 4/2011
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-011-1043-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Gene expression profiling of human hepatoblastoma using archived formalin-fixed and paraffin-embedded tissues

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2011

A subset of metzincins and related genes constitutes a marker of human solid organ fibrosis

Differentially expressed genes in giant cell tumor of bone

Analysis of select members of the E26 (ETS) transcription factors family in colorectal cancer

Precursor lesions of early onset pancreatic cancer

Diffuse lymphangiomatous hyperplasia of the spleen with hyaline bodies. A pseudotumoral proliferation arising from the lymphatic vessels of the periarteriolar lymphatic sheath

What is expected from the pathologist in the diagnosis of viral hepatitis?