Skip to main content
Log in

Frequent loss in chromosome 8p loci in liver cirrhosis accompanying hepatocellular carcinoma

  • Original Paper
  • Experimental Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Most hepatocellular carcinoma (HCC) is preceded by liver cirrhosis, but the genetic changes involved in cirrhosis are not well understood. We therefore studied loss of heterozygosity (LOH) in cirrhotic and neoplastic foci in livers of 14 patients with HCC. The samples, microdissected from paraffin-embedded tissues, were analyzed using a polymerase-chain-reaction-based assay for dinucleotide repeat polymorphisms on 8p. Of the 14 cases, 13 showed constitutional heterozygosity for the microsatellite markers. In 7 (54%) of these 13 informative cases, LOH was detected in the primary HCC and, in these 7 doubly informative (informative and LOH-positive in primary HCC) cases, LOH was found in 16 (70%) of 23 liver cirrhotic foci. The pattern of 8p allelic loss was identical in each doubly informative tumor; however, some of the liver cirrhotic foci harbored an 8p loss identical to that seen in the primary HCC, some harbored a different 8p loss, and some did not harbor any 8p loss. The remaining 6 cases without LOH on 8p in HCC showed no 8p loss in any cirrhotic foci. Presumably HCC could develop from cirrhotic cells harboring 8p loss.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

HCC :

hepatocellular carcinoma

LOH :

loss of heterozygosity

PCR :

polymerase chain reaction

AH :

adenomatous hyperplasia

AAH :

atypical adenomatous hyperplasia

References

  • Bergerheim USR, Kunimi K, Collins VP, Ekman P (1991) Deletion mapping of chromosomes 8, 10, and 16 in human prostatic carcinoma. Genes Chromosomes Cancer 3: 215–220

    PubMed  Google Scholar 

  • Buetow KH, Murray JC, Israel JL, London WT, Smith M, Kew M, Blanquet V, Brechot C, Redeker A, Govindarajah S (1989) Loss of heterozygosity suggests tumor suppressor gene responsible for primary hepatocellular carcinoma. Proc Natl Acad Sci USA 86:8852–8856

    PubMed  Google Scholar 

  • Ding S-F, Habib NA, Dooley J, Wood C, Bowles L, Delhanty JDA (1991) Loss of constitutional heterozygosity on chromosome 5q in hepatocellular carcinoma without cirrhosis. Br J Cancer 64:1083–1087

    PubMed  Google Scholar 

  • Emi M, Fujiwara Y, Nakajima T, Tsuchiya E, Tsuda H, Hirohashi S, Maeda Y, Tsuruka K, Miyaki M, Nakamura Y (1992) Frequent loss of heterozygosity for loci on chromosome 8p in hepatocellular carcinoma, colorectal cancer and lung cancer. Cancer Res 52:5368–5372

    PubMed  Google Scholar 

  • Fujimori M, Tokino T, Hino O, Kitagawa T, Imamura T, Okamoto E, Mitsunobu M, Ishikawa T, Nakagama H, Harada H, Yagura M, Matsubara K, Nakamura Y (1991) Allelotype study of primary hepatocellular carcinoma. Cancer Res 51:89–93

    PubMed  Google Scholar 

  • Fujimoto J, Okamoto B, Yamanaka N, Toyosaka A, Mitsunobu M (1991) Flow cytometric DNA analysis of hepatocellular carcinoma. Cancer 67:939–944

    PubMed  Google Scholar 

  • Fujiwara Y, Ohata H, Kuroki T, Koyama K, Tsuchiya E, Monden M, Nakamura Y (1995) Isolation of a candidate tumor suppressor gene on chromosome 8p21.3–p22 that is homologous to an extracellular domain of the PDGF receptor beta gene. Oncogene 10:891–896

    PubMed  Google Scholar 

  • Hung J, Kishimoto Y, Sugio K, Virmani A, McIntire DD, Minna JD, Gazdar AF (1995) Allele-specific specific chromosome 3p deletions occur at an early stage in the pathogenesis of lung carcinoma. JAMA 273:558–563

    PubMed  Google Scholar 

  • Ishizu H (1989) Flow cytometric analysis of the nuclear DNA content of hepatocellular carcinoma. Jpn J surg 19:662–673

    PubMed  Google Scholar 

  • Iwao Y, Kim YI, Kaketani K, Nakashima K, Okada K, Kobayashi M (1993) Stemline heterogeneity of nuclear DNA in hepatocellular carcinoma. Hepatogastroenterology 40:491–495

    PubMed  Google Scholar 

  • Kerangueven F, Essioux L, Dib A, Noguchi T, Allione F, Geneix J, Longy M, Lidereau R, Eisinger F, Pébusque M-J, Jacquemier J, Bonäti-Pellié C, Sobol H, Birnbaum D (1995) Loss of heterozygosity and linkage analysis in breast carcinoma: indication for a putative third susceptibility gene on the short arm of chromosome 8. Oncogene 10:1023–1026

    PubMed  Google Scholar 

  • Kishimoto Y, Sugio K, Hung JY, Virmani AK, McIntire DD, Minna JD, Gazdar AF (1995) Allele-specific loss in chromosome 9p loci in preneoplastic lesions accompanying non-small-cell lung cancers. J Natl Cancer Inst 87:1224–1229

    PubMed  Google Scholar 

  • Knowles MA, Shaw ME, Proctor AJ (1993) Deletion mapping of chromosome 8 in cancers of the urinary bladder using restriction length polymorphisms and microsatellite polymorphisms. Oncogene 8:1357–1364

    PubMed  Google Scholar 

  • Lerer I, Meiner V, Pashut-Lavon I, Abeliovich D (1994) Molecular diagnosis of Prader-Willi syndrome: Parent-of-origin dependent methylation sites and non-isotopic detection of (CA) n dinucleotide repeat polymorphisms. Am J Med Genet 52:79–84

    PubMed  Google Scholar 

  • Livni N, Eid A, Ilan Y, Rivkind A, Rosenmann E, Blendis LM, Shouval D, Galun E (1995) p53 expression in patients with cirrhosis with and without hepatocellular carcinoma. Cancer 75:2420–2426

    PubMed  Google Scholar 

  • Macoska JA, Trybus TM, Benson PD, Sakr WA, Grignon DJ, Wojno KD, Pietruk T, Powell IJ (1995) Evidence for three tumor suppressor gene on chromosome 8p in human prostate cancer. Cancer Res 55:5390–5395

    PubMed  Google Scholar 

  • Marshall CJ (1991) Tumor suppressor genes. Cell 64:313–326

    PubMed  Google Scholar 

  • McEntee GP, Batt KA, Kazmann JA, Ilstrup DM, Nagorney DM (1992) Relationship of nuclear DNA comtent to clinical and pathologic findings in patients with primary hepatic malignancy. Surgery 111:376–379

    PubMed  Google Scholar 

  • Miki Y, Nishisho I, Miyoshi Y, Utsunomiya J, Nakamura Y (1992) Interstitial loss of the same region of 5q in multiple adenomas and a carcinoma derived from an adenomatous polyposis coli (APC) patient. Genes Chromosomes Cancer 4:81–83

    PubMed  Google Scholar 

  • Murakami Y, Hayashi K, Hirohashi S, Sekiya T (1991) Aberrations of the tumor suppressor p53 and retinoblastoma genes in human hepatocellular carcinomas. Cancer Res 51:5520–5525

    PubMed  Google Scholar 

  • Nagasue N, Kohno H, Hayashi T, Yamanoi A, Uchida M, Takemoto Y (1993) Lack of intratumoral heterogeneity in DNA ploidy pattern of hepatocellular carcinoma. Gastroenterology 105:1449–1454

    PubMed  Google Scholar 

  • Nishida N, Fukuda Y, Kokuryu H, Sadamoto T, Isowa G, Honda K, Yamaoka Y, Ikenaga M, Imura H, Ishizaki K (1992) Accumulation of allele loss on arms of chromosomes 13q, 16q and 17p in the advanced stages of human hepatocellular carcinoma. Int J Cancer 52:862–868

    PubMed  Google Scholar 

  • O'Connell P, Pekkel V, Fuqua S, Osborne CK, Allred DC (1994) Molecular genetic studies of early breast cancer evolution. Breast Cancer Res Treat 32:5–12

    PubMed  Google Scholar 

  • Okada S, Ishii H, Nose H, Okusaka T, Kyogoku A, Yoshimori M, Sakamoto M, Hirohashi S (1995) Intratumoral DNA heterogeneity of small hepatocellular carcinoma. Cancer 75:444–450

    PubMed  Google Scholar 

  • Pääbo S (1989) Ancient DNA: extraction, characterization, molecular cloning, and enzymatic amplification. Proc Natl Acad Sci USA 86:1939–1943

    PubMed  Google Scholar 

  • Sakamoto M, Hirohashi S, Shimosato Y (1991) Early stages of multistep hepatocarcinogenesis: adenomatous hyperplasia and early hepatocellular carcinoma. Hum Pathol 22:172–178

    PubMed  Google Scholar 

  • Simon D, Knowles BB, Weith A (1991) Abnormalities of chromosome 1 and loss of heterozygosity on 1p in primary hepatomas. Oncogene 6:765–770

    PubMed  Google Scholar 

  • Sugio K, Kishimoto Y, Virmani AK, Hung JY, Gazdar AF (1994) K-ras mutations are a relatively late event in the pathogenesis of lung carcinomas. Cancer Res 54:5811–5815

    PubMed  Google Scholar 

  • Sundaresan V, Ganly P, Hasleton P, Rudd R, Sinha G, Bleehen NM, Rabbitts P (1992) p53 and chromosome 3 abnormalities, characteristic of malignant lung tumours, are detectable in preinvasive lesions of the bronchus. Oncogene 7:1989–1997

    PubMed  Google Scholar 

  • Takahashi K, Kudo J, Ishibashi H, Hirata Y, Niho Y (1993) Frequent loss of heterozygosity on chromosome 22 in hepatocellular carcinoma. Hepatology 17:794–799

    PubMed  Google Scholar 

  • Tanaka S, Toh Y, Adachi E, Matsumata T, Mori R, Sugimachi K (1993) Tumor progression in hepetocellular carcinoma may be mediated by p53 mutation. Cancer Res 53:2884–2887

    PubMed  Google Scholar 

  • Tsuda H, Zhang W, Shimosato Y, Yokota J, Terada M, Sugimura T, Miyamura T, Hirohashi S (1990) Allele loss on chromosome 16 associated with progression of human hepatocellular carcinoma. Proc Natl Acad Sci USA 87:6791–6794

    Google Scholar 

  • Walker GJ, Hayward NK, Falvey S, Cooksley WGE (1991) Loss of somatic heterozygosity in hepatocellular carcinoma. Cancer Res 51:4367–4370

    PubMed  Google Scholar 

  • Wang HP, Rogler CE (1988) Deletions in human chromosome arms 11p and 13q in primary hepatocellular carcinomas. Cytogenet Cell Genet 48:72–78

    PubMed  Google Scholar 

  • Wistuba II, Sugio K, Hung JY, Kishimoto Y, Virmani AK, Roa I, Albores-Saavedra J, Gazdar AF (1995) Allele-spacific mutations involved in the pathogenesis of endemic gallbladder carcinoma in Chile. Cancer Res 55:2511–2515

    PubMed  Google Scholar 

  • Zhang W, Hirohashi S, Tsuda H, Shimosato Y, Yokota J, Terada M, Sugimura T (1990) Frequent loss of heterozygosity on chromosomes 16 and 4 in human hepatocellular carcinoma. Jpn J Cancer Res 81:108–111

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kishimoto, Y., Shiota, G., Wada, K. et al. Frequent loss in chromosome 8p loci in liver cirrhosis accompanying hepatocellular carcinoma. J Cancer Res Clin Oncol 122, 585–589 (1996). https://doi.org/10.1007/BF01221189

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01221189

Key words

Navigation