Download Solid Tumour Section 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
Stevan Knezevich
BC Cancer Research Centre (BCCRC), Vancouver, British Columbia, Canada (SK)
Published in Atlas Database: June 2008
Online updated version : http://AtlasGeneticsOncology.org/Tumors/Livert1119inMHID5527.html
DOI: 10.4267/2042/44501
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2009 Atlas of Genetics and Cytogenetics in Oncology and Haematology
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.
Identity
Alias: Cystic hamartoma of the Liver; Cavernous
lymphangioadenomatoid tumor of the Liver; Benign
mesenchymoma of the Liver.
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.
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.
Embryonic origin
Mesoderm.
Etiology
Prognosis
Unknown.
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.
Epidemiology
Second most common liver tumor following hepatic
hemangiomas.
Pathology
Unknown. There are several possibilities with
Atlas Genet Cytogenet Oncol Haematol. 2009; 13(6)
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Liver: t(11;19)(q11;q13.4) (MALAT-1/MLHB1) in Mesenchymal Hamartoma of the Liver
Knezevich S
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.
MALAT1 (metastasis associated lung
adenocarcinoma transcript 1 (nonprotein coding))
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.
Atlas Genet Cytogenet Oncol Haematol. 2009; 13(6)
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
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Liver: t(11;19)(q11;q13.4) (MALAT-1/MLHB1) in Mesenchymal Hamartoma of the Liver
Knezevich S
Rakheja D, Margraf LR, Tomlinson GE, Schneider NR. Hepatic
mesenchymal hamartoma with translocation involving
chromosome band 19q13.4: a recurrent abnormality. Cancer
Genet Cytogenet. 2004 Aug;153(1):60-3
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.
Yamada K, Kano J, Tsunoda H, Yoshikawa H, Okubo C,
Ishiyama T, Noguchi M. Phenotypic characterization of
endometrial stromal sarcoma of the uterus. Cancer Sci. 2006
Feb;97(2):106-12
Fellenberg J, Bernd L, Delling G, Witte D, ZahltenHinguranage A. Prognostic significance of drug-regulated
genes in high-grade osteosarcoma. Mod Pathol. 2007
Oct;20(10):1085-94
References
Lin R, Maeda S, Liu C, Karin M, Edgington TS. A large
noncoding RNA is a marker for murine hepatocellular
carcinomas and a spectrum of human carcinomas. Oncogene.
2007 Feb 8;26(6):851-8
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. Cloning of an Alpha-TFEB fusion in
renal tumors harboring the t(6;11)(p21;q13) chromosome
translocation. Proc Natl Acad Sci U S A. 2003 May
13;100(10):6051-6
Pecciarini L, Cangi MG, Lo Cunsolo C, Macri' E, Dal Cin E,
Martignoni G, Doglioni C. Characterization of t(6;11)(p21;q12)
in a renal-cell carcinoma of an adult patient. Genes
Chromosomes Cancer. 2007 May;46(5):419-26
Rajaram V, Knezevich S, Bove KE, Perry A, Pfeifer JD. 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. Genes
Chromosomes Cancer. 2007 May;46(5):508-13
Ji P, Diederichs S, Wang W, Böing S, Metzger R, Schneider
PM, Tidow N, Brandt B, Buerger H, Bulk E, Thomas M, Berdel
WE, Serve H, Müller-Tidow C. MALAT-1, a novel noncoding
RNA, and thymosin beta4 predict metastasis and survival in
early-stage non-small cell lung cancer. Oncogene. 2003 Sep
11;22(39):8031-41
Perez DS, Hoage TR, Pritchett JR, Ducharme-Smith AL,
Halling ML, Ganapathiraju SC, Streng PS, Smith DI. Long,
abundantly expressed non-coding transcripts are altered in
cancer. Hum Mol Genet. 2008 Mar 1;17(5):642-55
Kuiper RP, Schepens M, Thijssen J, van Asseldonk M, van
den Berg E, Bridge J, Schuuring E, Schoenmakers EF, van
Kessel AG. Upregulation of the transcription factor TFEB in
t(6;11)(p21;q13)-positive renal cell carcinomas due to promoter
substitution. Hum Mol Genet. 2003 Jul 15;12(14):1661-9
This article 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. 2009; 13(6):445-447.
Müller-Tidow C, Diederichs S, Thomas M, Serve H. Genomewide screening for prognosis-predicting genes in early-stage
non-small-cell lung cancer. Lung Cancer. 2004 Aug;45 Suppl
2:S145-50
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