Liver: t(11;19)(q11;q13.4) (MALAT-1/MLHB1) in Mesenchymal Hamartoma of the Liver

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Liver: t(11;19)(q11;q13.4) (MALAT-1/MLHB1) in Mesenchymal Hamartoma of the Liver

Identity

Other names Cystic hamartoma of the Liver
Cavernous lymphangioadenomatoid tumor of the Liver
Benign mesenchymoma of the Liver

A) Low power view showing a benign proliferation of abnormally branched bile ducts, with no atypical features, amongst a loose myxoid background. Also seen in this view are numerous mesenchymal cells with cleared cytoplasm and small, hyperchromatic nuclei. B) Higher power view showing the abnormally branched bile ducts and mesenchymal cells.

Classification

Note It represents the second most common benign liver tumor, but its role as a malignant precursor is still not clear.

Clinics and Pathology

Disease The tumor affects both males and females equally and is a disease that is predominantly seen in newborns although rare adult cases have also been reported. Two basic morphologies exist; cystic and solid. Cystic MHL is most common, followed by solid, then a mixture of cystic and solid, and finally, angiomatous.

Embryonic origin Mesoderm

Etiology Unknown

Epidemiology Second most common liver tumor following hepatic hemangiomas.

Pathology Unknown. There are several possibilities with regards to the pathophysiology of MHL. One should always consider the possibility that the recurring translocation has little or nothing to do with tumor formation, but is rather found as a secondary phenomenon. If we assume that the translocation product is responsible, then the following possibilities exist:

The MALAT-1 gene is disrupted by the translocation and not allowed to perform its usual functions. This leaves one functional copy per cell, which may not be enough. Alternatively, the derivative MALAT product may interfere with the wild type gene product.
The MALAT-1 gene gains a new function or loses regulatory function by the loss of either the 5' or 3' half of the original gene product.
There is a novel translocation product produced with an as of yet to be determined gene product on chromosome 19.

Treatment Surgical resection remains the mainstay of treatment. Other accounts of cyst aspiration in utero have been documented with mixed results. When possible, a watch and wait approach has also been employed, since these tumors tend to spontaneously regress over time.

Prognosis When there is complete resection of the tumor, the prognosis is excellent. When aspiration or watching and waiting are the primary means of "treatment", then the prognosis is not as clear cut and is evaluated on a case by case basis.

Genes involved and Proteins

Note MALAT-1 and MHLB1. The latter is not a gene per se, but rather a breakpoint located on chromosome 19. It is unclear as of yet, whether the breakpoint occurs in a novel gene or whether it serves to disrupt MALAT-1 through a translocation event. If MALAT-1 is the 5' end of the translocation product, then no protein is expected from such a fusion as MALAT-1 is not translated. If there is a gene within the chromosome 19 breakpoint and it acts as the 5' end of the novel translocation product, then the possibility of a novel protein exists.

Gene Name MALAT1 (metastasis associated lung adenocarcinoma transcript 1 (non-protein coding))

Location 11q13.1

Note MALAT-1 was initially found as an overexpressed molecule in lung adenocarcinomas. It is normally expressed in a wide variety of tissues with some of the highest levels of expression found in the pancreas. It was found to be rearranged in a subset of renal cell carcinomas harboring the t(6;11)(p21;q13). Recent studies have found MALAT-1 to be overexpressed in a number of carcinomas, endometrial stromal sarcomas of the uterus, and its expression can be used to monitor response to chemotherapy in osteosarcomas.

Dna / Rna Two isoforms have been discovered. The short isoform is 8110 bp while the long isoform is 8352 bp. Both isoforms harbor a splice site at the 5' end, while the short isoform has an additional splice site near the middle that results in a shorter overall product.

Protein Non-translated RNA product.

Bibliography

Cloning of an Alpha-TFEB fusion in renal tumors harboring the t(6;11)(p21;q13) chromosome translocation.

Davis IJ, Hsi BL, Arroyo JD, Vargas SO, Yeh YA, Motyckova G, Valencia P, Perez-Atayde AR, Argani P, Ladanyi M, Fletcher JA, Fisher DE.

Proc Natl Acad Sci U S A. 2003 May 13;100(10):6051-6. Epub 2003 Apr 28.

PMID 12719541

MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer.

Ji P, Diederichs S, Wang W, Boing S, Metzger R, Schneider PM, Tidow N, Brandt B, Buerger H, Bulk E, Thomas M, Berdel WE, Serve H, Muller-Tidow C.

Oncogene. 2003 Sep 11;22(39):8031-41.

PMID 12970751

Upregulation of the transcription factor TFEB in t(6;11)(p21;q13)-positive renal cell carcinomas due to promoter substitution.

Kuiper RP, Schepens M, Thijssen J, van Asseldonk M, van den Berg E, Bridge J, Schuuring E, Schoenmakers EF, van Kessel AG.

Hum Mol Genet. 2003 Jul 15;12(14):1661-9.

PMID 12837690

Genome-wide screening for prognosis-predicting genes in early-stage non-small-cell lung cancer.

Muller-Tidow C, Diederichs S, Thomas M, Serve H.

Lung Cancer. 2004 Aug;45 Suppl 2:S145-50.

PMID 15552795

Hepatic mesenchymal hamartoma with translocation involving chromosome band 19q13.4: a recurrent abnormality.

Rakheja D, Margraf LR, Tomlinson GE, Schneider NR.

Cancer Genet Cytogenet. 2004 Aug;153(1):60-3.

PMID 15325096

Phenotypic characterization of endometrial stromal sarcoma of the uterus.

Yamada K, Kano J, Tsunoda H, Yoshikawa H, Okubo C, Ishiyama T, Noguchi M.

Cancer Sci. 2006 Feb;97(2):106-12.

PMID 16441420

Prognostic significance of drug-regulated genes in high-grade osteosarcoma.

Fellenberg J, Bernd L, Delling G, Witte D, Zahlten-Hinguranage A.

Mod Pathol. 2007 Oct;20(10):1085-94. Epub 2007 Jul 27.

PMID 17660802

A large noncoding RNA is a marker for murine hepatocellular carcinomas and a spectrum of human carcinomas.

Lin R, Maeda S, Liu C, Karin M, Edgington TS.

Oncogene. 2007 Feb 8;26(6):851-8. Epub 2006 Jul 31.

PMID 16878148

Characterization of t(6;11)(p21;q12) in a renal-cell carcinoma of an adult patient.

Pecciarini L, Cangi MG, Lo Cunsolo C, Macri' E, Dal Cin E, Martignoni G, Doglioni C.

Genes Chromosomes Cancer. 2007 May;46(5):419-26.

PMID 17285572

DNA sequence of the translocation breakpoints in undifferentiated embryonal sarcoma arising in mesenchymal hamartoma of the liver harboring the t(11;19)(q11;q13.4) translocation.

Rajaram V, Knezevich S, Bove KE, Perry A, Pfeifer JD.

Genes Chromosomes Cancer. 2007 May;46(5):508-13.

PMID 17311249

Long, abundantly expressed non-coding transcripts are altered in cancer.

Perez DS, Hoage TR, Pritchett JR, Ducharme-Smith AL, Halling ML, Ganapathiraju SC, Streng PS, Smith DI.

Hum Mol Genet. 2008 Mar 1;17(5):642-55. Epub 2007 Nov 15.

PMID 18006640

REVIEW articles automatic search in PubMed

Last year publications automatic search in PubMed

Contributor(s)

Written 06-2008 Stevan Knezevich

BC Cancer Research Centre (BCCRC), Vancouver, British Columbia, Canada

Citation

This paper should be referenced as such :
Knezevich S . Liver: t(11;19)(q11;q13.4) (MALAT-1/MLHB1) in Mesenchymal Hamartoma of the Liver. Atlas Genet Cytogenet Oncol Haematol. June 2008 .
URL : http://AtlasGeneticsOncology.org/Genes/Livert1119inMHID5527.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Wed Sep 24 21:08:55 2008

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For comments and suggestions or contributions, please contact us

j.l.huret@chu-poitiers.fr.

Other names	Cystic hamartoma of the Liver
	Cavernous lymphangioadenomatoid tumor of the Liver
	Benign mesenchymoma of the Liver


	A) Low power view showing a benign proliferation of abnormally branched bile ducts, with no atypical features, amongst a loose myxoid background. Also seen in this view are numerous mesenchymal cells with cleared cytoplasm and small, hyperchromatic nuclei. B) Higher power view showing the abnormally branched bile ducts and mesenchymal cells.

Disease	The tumor affects both males and females equally and is a disease that is predominantly seen in newborns although rare adult cases have also been reported. Two basic morphologies exist; cystic and solid. Cystic MHL is most common, followed by solid, then a mixture of cystic and solid, and finally, angiomatous.
Embryonic origin	Mesoderm
Etiology	Unknown
Epidemiology	Second most common liver tumor following hepatic hemangiomas.
Pathology	Unknown. There are several possibilities with regards to the pathophysiology of MHL. One should always consider the possibility that the recurring translocation has little or nothing to do with tumor formation, but is rather found as a secondary phenomenon. If we assume that the translocation product is responsible, then the following possibilities exist: The MALAT-1 gene is disrupted by the translocation and not allowed to perform its usual functions. This leaves one functional copy per cell, which may not be enough. Alternatively, the derivative MALAT product may interfere with the wild type gene product. The MALAT-1 gene gains a new function or loses regulatory function by the loss of either the 5' or 3' half of the original gene product. There is a novel translocation product produced with an as of yet to be determined gene product on chromosome 19.
Treatment	Surgical resection remains the mainstay of treatment. Other accounts of cyst aspiration in utero have been documented with mixed results. When possible, a watch and wait approach has also been employed, since these tumors tend to spontaneously regress over time.
Prognosis	When there is complete resection of the tumor, the prognosis is excellent. When aspiration or watching and waiting are the primary means of "treatment", then the prognosis is not as clear cut and is evaluated on a case by case basis.

Gene Name	MALAT1 (metastasis associated lung adenocarcinoma transcript 1 (non-protein coding))
Location	11q13.1
Note	MALAT-1 was initially found as an overexpressed molecule in lung adenocarcinomas. It is normally expressed in a wide variety of tissues with some of the highest levels of expression found in the pancreas. It was found to be rearranged in a subset of renal cell carcinomas harboring the t(6;11)(p21;q13). Recent studies have found MALAT-1 to be overexpressed in a number of carcinomas, endometrial stromal sarcomas of the uterus, and its expression can be used to monitor response to chemotherapy in osteosarcomas.
Dna / Rna	Two isoforms have been discovered. The short isoform is 8110 bp while the long isoform is 8352 bp. Both isoforms harbor a splice site at the 5' end, while the short isoform has an additional splice site near the middle that results in a shorter overall product.
Protein	Non-translated RNA product.

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

Written	06-2008	Stevan Knezevich
		BC Cancer Research Centre (BCCRC), Vancouver, British Columbia, Canada