Allele Loss on Chromosome 16 Associated with Progression of Human Hepatocellular Carcinoma

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1990 Sep 1

PMID 2168560

Citations 65

Authors

H Tsuda

W D Zhang

Y Shimosato

J Yokota

M Terada

T Sugimura

T Miyamura

S Hirohashi

Affiliations

Soon will be listed here.

Abstract

Loss of heterozygosity on chromosome 16 is a common genetic alteration in human hepatocellular carcinoma (HCC). To clarify the pathogenetic significance of allele loss on chromosome 16, we performed restriction fragment length polymorphism analysis of 70 surgically resected tumors by using 15 polymorphic DNA markers for chromosome 16. Loss of heterozygosity on chromosome 16 was detected in 36 (52%) of 69 informative cases, and the common region of allele loss in these 36 tumors was located between the HP locus (16q22.1) and the CTRB locus (16q22.3-q23.2). These losses occurred more frequently in HCCs of poor differentiation, of larger size, and with metastasis, whereas they were not detected in HCC at the earliest stage. In addition, these losses were not associated with presence or absence of hepatitis B virus DNA integration or hepatitis C virus infection. These results show that loss of heterozygosity on chromosome 16 is a late event occurring after hepatocarcinogenesis and strongly suggest that this phenomenon is involved in enhancement of tumor aggressiveness during progression of HCC.

Citing Articles

Machine learning and multi-omics data reveal driver gene-based molecular subtypes in hepatocellular carcinoma for precision treatment.

Wang M, Yan X, Dong Y, Li X, Gao B PLoS Comput Biol. 2024; 20(5):e1012113.

PMID: 38728362 PMC: 11230636. DOI: 10.1371/journal.pcbi.1012113.

Molecular pathological approach to cancer epigenomics and its clinical application.

Kanai Y Pathol Int. 2024; 74(4):167-186.

PMID: 38482965 PMC: 11551818. DOI: 10.1111/pin.13418.

Integrated Analysis of Ulcerative Colitis Revealed an Association between and Immune Infiltration.

Li T, Liu W, Hui W, Shi T, Liu H, Feng Y Dis Markers. 2022; 2022:4983471.

PMID: 35308140 PMC: 8931176. DOI: 10.1155/2022/4983471.

PHLPPing the Script: Emerging Roles of PHLPP Phosphatases in Cell Signaling.

Baffi T, Cohen-Katsenelson K, Newton A Annu Rev Pharmacol Toxicol. 2020; 61:723-743.

PMID: 32997603 PMC: 11003498. DOI: 10.1146/annurev-pharmtox-031820-122108.

Prognostic significance of kynurenine 3-monooxygenase and effects on proliferation, migration, and invasion of human hepatocellular carcinoma.

Jin H, Zhang Y, You H, Tao X, Wang C, Jin G Sci Rep. 2015; 5:10466.

PMID: 26099564 PMC: 4479133. DOI: 10.1038/srep10466.

References

Buetow K, Murray J, Israel J, London W, Smith M, Kew M . Loss of heterozygosity suggests tumor suppressor gene responsible for primary hepatocellular carcinoma. Proc Natl Acad Sci U S A. 1989; 86(22):8852-6. PMC: 298388. DOI: 10.1073/pnas.86.22.8852. View

Saito I, Miyamura T, Ohbayashi A, Harada H, Katayama T, Kikuchi S . Hepatitis C virus infection is associated with the development of hepatocellular carcinoma. Proc Natl Acad Sci U S A. 1990; 87(17):6547-9. PMC: 54573. DOI: 10.1073/pnas.87.17.6547. View

Nigro J, Baker S, Preisinger A, Jessup J, Hostetter R, Cleary K . Mutations in the p53 gene occur in diverse human tumour types. Nature. 1989; 342(6250):705-8. DOI: 10.1038/342705a0. View

Fearon E, Cho K, Nigro J, Kern S, Simons J, Ruppert J . Identification of a chromosome 18q gene that is altered in colorectal cancers. Science. 1990; 247(4938):49-56. DOI: 10.1126/science.2294591. View

Miyamura T, Saito I, Katayama T, Kikuchi S, Tateda A, Houghton M . Detection of antibody against antigen expressed by molecularly cloned hepatitis C virus cDNA: application to diagnosis and blood screening for posttransfusion hepatitis. Proc Natl Acad Sci U S A. 1990; 87(3):983-7. PMC: 53394. DOI: 10.1073/pnas.87.3.983. View

Arthur D, Bloomfield C . Partial deletion of the long arm of chromosome 16 and bone marrow eosinophilia in acute nonlymphocytic leukemia: a new association. Blood. 1983; 61(5):994-8. View

Le Beau M, Larson R, Bitter M, Vardiman J, Golomb H, Rowley J . Association of an inversion of chromosome 16 with abnormal marrow eosinophils in acute myelomonocytic leukemia. A unique cytogenetic-clinicopathological association. N Engl J Med. 1983; 309(11):630-6. DOI: 10.1056/NEJM198309153091103. View

Cavenee W, Dryja T, Phillips R, Benedict W, Godbout R, Gallie B . Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. Nature. 1983; 305(5937):779-84. DOI: 10.1038/305779a0. View

Maeda N, Yang F, Barnett D, BOWMAN B, SMITHIES O . Duplication within the haptoglobin Hp2 gene. Nature. 1984; 309(5964):131-5. DOI: 10.1038/309131a0. View

10.

Bell G, Quinto C, Quiroga M, Valenzuela P, Craik C, Rutter W . Isolation and sequence of a rat chymotrypsin B gene. J Biol Chem. 1984; 259(22):14265-70. View

11.

Kobayashi M, Koike K . Complete nucleotide sequence of hepatitis B virus DNA of subtype adr and its conserved gene organization. Gene. 1984; 30(1-3):227-32. DOI: 10.1016/0378-1119(84)90124-0. View

12.

Murray A, Drobetsky E, Arrand J . Cloning the complete human adenine phosphoribosyl transferase gene. Gene. 1984; 31(1-3):233-40. DOI: 10.1016/0378-1119(84)90214-2. View

13.

Assum G, Griese E, Horst J . Detection of a restriction site polymorphism within the human alpha-globin gene complex. Hum Genet. 1985; 69(2):144-6. DOI: 10.1007/BF00293285. View

14.

Knudson Jr A . Hereditary cancer, oncogenes, and antioncogenes. Cancer Res. 1985; 45(4):1437-43. View

15.

Tiollais P, Pourcel C, Dejean A . The hepatitis B virus. Nature. 1985; 317(6037):489-95. DOI: 10.1038/317489a0. View

16.

Rogler C, Sherman M, Su C, Shafritz D, Summers J, Shows T . Deletion in chromosome 11p associated with a hepatitis B integration site in hepatocellular carcinoma. Science. 1985; 230(4723):319-22. DOI: 10.1126/science.2996131. View

17.

Friend S, Bernards R, Rogelj S, Weinberg R, Rapaport J, Albert D . A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature. 1986; 323(6089):643-6. DOI: 10.1038/323643a0. View

18.

Bufton L, Mohandas T, Magenis R, Sheehy R, Bestwick R, Litt M . A highly polymorphic locus on chromosome 16q revealed by a probe from a chromosome-specific cosmid library. Hum Genet. 1986; 74(4):425-31. DOI: 10.1007/BF00280499. View

19.

Hyland V, Grist S, West A, Richards R, Sutherland G . A 5' flanking region of the metallothionein, MT2A, gene identifies two moderately frequent RFLPs. Nucleic Acids Res. 1987; 15(3):1350. PMC: 340548. DOI: 10.1093/nar/15.3.1350. View

20.

KENMOCHI K, Sugihara S, Kojiro M . Relationship of histologic grade of hepatocellular carcinoma (HCC) to tumor size, and demonstration of tumor cells of multiple different grades in single small HCC. Liver. 1987; 7(1):18-26. DOI: 10.1111/j.1600-0676.1987.tb00310.x. View