t(1;1)(p36;q21) in Non Hodgkin Lymphoma

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t(1;1)(p36;q21) in Non Hodgkin Lymphoma

Identity

.Unbalanced t(1;1)(p36;q21) in NHL with dup(q21q44) as observed by, G-band, M-FISH and M-BAND [ISCN2005: der(1)t(p36.3;q21.1-2)dup(1)(q21.1-2q44)].

Clinics and Pathology

Disease Non Hodgkin Lymphoma (NHL). Aberrations of chromosomal bands 1p36 and 1q11-q23 are among the most common chromosomal alterations in NHL.

Phenotype / cell stem origin Lymphocytes (B-cell and T-cell).

Etiology The exact etiology of NHL is still unknown, risk increases with exposed to ionizing radiation, chemicals such as pesticides or solvents, Epstein-Barr Virus infection, family history of NHL (although no hereditary pattern has been established, Human Immunodeficiency Virus (HIV) infection, immunosuppression or immunodeficiency, genetics.

Epidemiology NHL is the 5th most frequently diagnosed cancer overall for both males and females, males are slightly more often affected than females, increasing over time.

Clinics At diagnosis, painful swelling of lymph nodes located in the neck, underarm and groin, unexplained fever, night sweats, constant fatigue, unexplained weight loss, itchy skin.

Cytology Anti-B-cell antibodies (e.g. CD19, CD20, CD10, CD23); anti-T-cell antibodies (e.g. CD3, CD4, CD2/HLADR); other antibodies (e.g. CD45 for total lymphocytes, CD10 for monocytes).

Transformed follicular lymphoma (courtesy, Dr. R.D. Gascoyne, BC Cancer Agency, Vancouver, Canada).

Pathology t(1;1)(p36;q21) has been seen in following NHL types as characterized by pathology; follicular lymphoma (FL) grades 1-3; diffuse large B-cell lymphoma; T-cell lymphoma and peripheral T-cell lymphoma.

Univariate analyses using the Kaplan-Meier method for 1p36-, demonstrating the significance of this chromosomal change for overall survival. In multivariate analysis using the Cox regression model controlling for IPI, the significance remained intact.

Treatment Depend on the stage and type and genetics of NHL; "watch-and-wait" approach in case of indolent follicular lymphomas; radiotherapy to site of problem; systemic chemotherapy; oral agents; IV agents; antibody against CD20; stem cell or bone marrow transplant.

Evolution Initial genomic aberration (such as t(14;18)(q32;q21) in follicular lymphoma) may or may not be sufficient for the initiation of the malignant phenotype. Additional genomic rearrangements are required for disease progression.

Prognosis Depend on the stage, type and genetics of NHL; in general, highly treatable and some times curable. However, a number of karyotype parameters have been reported to influence prognosis in NHL. It has been demonstrated that the cytogenetic abnormality 1p36-, as a result of t(1;1)(p36;q21) or another rearrangement involving chromosome 1, was found to be a significant predictors of adverse overall survival for FL (univariate and multivariate analysis).

Genetics

Initial cytogenetic changes often seen in e.g. FL and t(14;18)(q32;q21) (/BCL2); DLBL and t(3;14)(q27;q21)(BCL6/IGH). Additional acquired mutations are necessary to generate a fully malignant clonal proliferation. Many of these secondary genetic alterations (including chromosome 1) are visible in the clonal karyotype; it is now possible to identify the sequence by which they arise and their influence on clinical behavior by using computational methods to manipulate complex chromosomal data in large number of cases.

Cytogenetics

Note t(1;1)(p36;q21). G-band and M-BAND1 Detection of der(1)t(1;1).

Cytogenetics Morphological Normal chromosome 1 with derivative chromosomes 1; Breakpoints are at chromosomal positions 1p36.3 and 1q21.1-2; duplication of the 1q21 to 1q44; adverse prognosis (?as a result of 1p36 suppressor genes deletions and/or duplication of 1q21q44 oncogenes); additional secondary abnormalities to t(1;1) of various complexity as usually seen in NHL.

A: The derivative chromosome 1 in all 16 NHL cases as seen by G-band analysis. Arrows indicate the additional unidentified dark band.
B: The corresponding derivative chromosome 1 as seen by M-BAND1 analysis. Arrows indicate the dup(1)(q21.1q21.2) at the p/q-arm interface (broad orange/ pink bands). X indicates cases where no material was available for M-BAND1 analysis.
C: Normal chromosome 1 as seen by G-band and M-BAND1 analysis, color classifier, and ISCN 550-band level ideogram.

Cytogenetics Molecular LS-FISH identification of 1p36.3 and 1q21.1-2 breakpoints on der(1)t(1;1); Two distinct types of 1p36.3 rearrangements were observed: One type involved deletions of SKI, MEL1, and TP73, and retained CASP9 the other type showed breakpoints telomeric to TP73; Four distinct types of 1q21.1-2 rearrangements were observed: The first type involved breakpoints at IRTA1 and IRTA2 with duplications of IRTA1, IRTA2, BCL9, AF1Q, JTB, and MUC1; the second type involved a breakpoint at BCL9 with duplications of BCL9, AF1Q, JTB, and MUC1; the third type involved a breakpoint at AF1Q with duplications of AF1Q, JTB, and MUC1; the fourth type involved an undefined breakpoint telomeric to MUC1.

Composite picture of all LS-FISH patterns observed in this study with representative examples.
A: Normal color-coded chromosome 1 LS-FISH pattern, demonstrating the relative localization of all BAC probes.
B: All der(1)t(1;1) combinations seen by LS-FISH.
C: Two color-coded representative images corresponding to B and demonstrating the p/q-arm breakpoint interfaces.

Genes involved and Proteins

Note The remarkable frequency of centromeric/pericentromeric rearrangements of chromosome 1 in B-cell malignancies has been clearly associated with tumor progression. A factor in the pathology associated with the centromeric/pericentromeric region 1q10-12 is a sequence-specific DNA-binding protein called Ikaros that is speculated to be essential for lymphocyte development. Methylation, interactions with proteins interfering with heterochromatin, and possible gene silencing attributed to heterochromatin may be responsible as well. The mechanisms, however, underlying the formation of recurring chromosome 1 aberrations in many hematological malignancies and the consequences of these various chromosomal rearrangements are largely undetermined.
Conserved Homology for 1p36 and 1q21?
It has been speculated that 1q21, 1p11-12, and 1p36 are evolutionarily conserved and that the homology between these regions is associated with chromosomal instability. A mechanism of homologous recombination may be in place that would explain the frequent chromosome 1 rearrangements involving 1p36, 1p11-12, and 1q21, but wouldn't explain the various breakpoints seen in these regions.

Translocations implicated (Data extracted from papers in the Atlas)

t(1;1)(p36;q21) in Non Hodgkin Lymphoma

External links

Mitelman database Mitelman database (CGAP - NCBI)
t(1;1)(p36;q21) - Mitelman database (CGAP - NCBI)

Bibliography

Uncovering novel inter- and intrachromosomal chromosome 1 aberrations in follicular lymphomas by using an innovative multicolor banding technique.

Lestou VS, Gascoyne RD, Salski C, Connors JM, Horsman DE

Genes, chromosomes & cancer. 2002 ; 34 (2) : 201-210.

PMID 11979554

Multicolour fluorescence in situ hybridization analysis of t(14;18)-positive follicular lymphoma and correlation with gene expression data and clinical outcome.

Lestou VS, Gascoyne RD, Sehn L, Ludkovski O, Chhanabhai M, Klasa RJ, Husson H, Freedman AS, Connors JM, Horsman DE

British journal of haematology. 2003 ; 122 (5) : 745-759.

PMID 12930384

Follicular lymphoma lacking the t(14;18)(q32;q21): identification of two disease subtypes.

Horsman DE, Okamoto I, Ludkovski O, Le N, Harder L, Gesk S, Siebert R, Chhanabhai M, Sehn L, Connors JM, Gascoyne RD

British journal of haematology. 2003 ; 120 (3) : 424-433.

PMID 12580956

Characterization of the recurrent translocation t(1;1)(p36.3;q21.1-2) in non-Hodgkin lymphoma by multicolor banding and fluorescence in situ hybridization analysis.

Lestou VS, Ludkovski O, Connors JM, Gascoyne RD, Lam WL, Horsman DE

Genes, chromosomes & cancer. 2003 ; 36 (4) : 375-381.

PMID 12619161

Identification of cytogenetic subgroups and karyotypic pathways of clonal evolution in follicular lymphomas.

Hˆglund M, Sehn L, Connors JM, Gascoyne RD, Siebert R, Sˆ§ll T, Mitelman F, Horsman DE

Genes, chromosomes & cancer. 2004 ; 39 (3) : 195-204.

PMID 14732921

New insights into the evolution of chromosome 1.

Weise A, Starke H, Mrasek K, Claussen U, Liehr T

Cytogenetic and genome research. 2005 ; 108 (1-3) : 217-222.

PMID 15545733

REVIEW articles automatic search in PubMed

Last year articles automatic search in PubMed

Contributor(s)

Written 06-2006 Valia S Lestou

The Hospital for Sick Kids, Dept. Paediatric Laboratory Medicine (DPLM), 555 University Ave, Toronto, ON M5G 1X8, Canada

Citation

This paper should be referenced as such :

Lestou, VS

t(1;1)(p36;q21) in non Hodgkin lymphoma

Atlas Genet Cytogenet Oncol Haematol. 2006;10(4):272-275.

Free online version Free pdf version [Bibliographic record ]

URL : http://AtlasGeneticsOncology.org/Anomalies/t0101p36q21ID1431.html

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indexed on : Fri Jul 11 13:08:04 CEST 2014

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Disease	Non Hodgkin Lymphoma (NHL). Aberrations of chromosomal bands 1p36 and 1q11-q23 are among the most common chromosomal alterations in NHL.
Phenotype / cell stem origin	Lymphocytes (B-cell and T-cell).
Etiology	The exact etiology of NHL is still unknown, risk increases with exposed to ionizing radiation, chemicals such as pesticides or solvents, Epstein-Barr Virus infection, family history of NHL (although no hereditary pattern has been established, Human Immunodeficiency Virus (HIV) infection, immunosuppression or immunodeficiency, genetics.
Epidemiology	NHL is the 5th most frequently diagnosed cancer overall for both males and females, males are slightly more often affected than females, increasing over time.
Clinics	At diagnosis, painful swelling of lymph nodes located in the neck, underarm and groin, unexplained fever, night sweats, constant fatigue, unexplained weight loss, itchy skin.
Cytology	Anti-B-cell antibodies (e.g. CD19, CD20, CD10, CD23); anti-T-cell antibodies (e.g. CD3, CD4, CD2/HLADR); other antibodies (e.g. CD45 for total lymphocytes, CD10 for monocytes).


	Transformed follicular lymphoma (courtesy, Dr. R.D. Gascoyne, BC Cancer Agency, Vancouver, Canada).

Pathology	t(1;1)(p36;q21) has been seen in following NHL types as characterized by pathology; follicular lymphoma (FL) grades 1-3; diffuse large B-cell lymphoma; T-cell lymphoma and peripheral T-cell lymphoma.


	Univariate analyses using the Kaplan-Meier method for 1p36-, demonstrating the significance of this chromosomal change for overall survival. In multivariate analysis using the Cox regression model controlling for IPI, the significance remained intact.

Treatment	Depend on the stage and type and genetics of NHL; "watch-and-wait" approach in case of indolent follicular lymphomas; radiotherapy to site of problem; systemic chemotherapy; oral agents; IV agents; antibody against CD20; stem cell or bone marrow transplant.
Evolution	Initial genomic aberration (such as t(14;18)(q32;q21) in follicular lymphoma) may or may not be sufficient for the initiation of the malignant phenotype. Additional genomic rearrangements are required for disease progression.
Prognosis	Depend on the stage, type and genetics of NHL; in general, highly treatable and some times curable. However, a number of karyotype parameters have been reported to influence prognosis in NHL. It has been demonstrated that the cytogenetic abnormality 1p36-, as a result of t(1;1)(p36;q21) or another rearrangement involving chromosome 1, was found to be a significant predictors of adverse overall survival for FL (univariate and multivariate analysis).

Note	t(1;1)(p36;q21). G-band and M-BAND1 Detection of der(1)t(1;1).
Cytogenetics Morphological	Normal chromosome 1 with derivative chromosomes 1; Breakpoints are at chromosomal positions 1p36.3 and 1q21.1-2; duplication of the 1q21 to 1q44; adverse prognosis (?as a result of 1p36 suppressor genes deletions and/or duplication of 1q21q44 oncogenes); additional secondary abnormalities to t(1;1) of various complexity as usually seen in NHL.


	A: The derivative chromosome 1 in all 16 NHL cases as seen by G-band analysis. Arrows indicate the additional unidentified dark band. B: The corresponding derivative chromosome 1 as seen by M-BAND1 analysis. Arrows indicate the dup(1)(q21.1q21.2) at the p/q-arm interface (broad orange/ pink bands). X indicates cases where no material was available for M-BAND1 analysis. C: Normal chromosome 1 as seen by G-band and M-BAND1 analysis, color classifier, and ISCN 550-band level ideogram.

Cytogenetics Molecular	LS-FISH identification of 1p36.3 and 1q21.1-2 breakpoints on der(1)t(1;1); Two distinct types of 1p36.3 rearrangements were observed: One type involved deletions of SKI, MEL1, and TP73, and retained CASP9 the other type showed breakpoints telomeric to TP73; Four distinct types of 1q21.1-2 rearrangements were observed: The first type involved breakpoints at IRTA1 and IRTA2 with duplications of IRTA1, IRTA2, BCL9, AF1Q, JTB, and MUC1; the second type involved a breakpoint at BCL9 with duplications of BCL9, AF1Q, JTB, and MUC1; the third type involved a breakpoint at AF1Q with duplications of AF1Q, JTB, and MUC1; the fourth type involved an undefined breakpoint telomeric to MUC1.


	Composite picture of all LS-FISH patterns observed in this study with representative examples. A: Normal color-coded chromosome 1 LS-FISH pattern, demonstrating the relative localization of all BAC probes. B: All der(1)t(1;1) combinations seen by LS-FISH. C: Two color-coded representative images corresponding to B and demonstrating the p/q-arm breakpoint interfaces.

Mitelman database	Mitelman database (CGAP - NCBI)
	t(1;1)(p36;q21) - Mitelman database (CGAP - NCBI)

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

Written	06-2006	Valia S Lestou
		The Hospital for Sick Kids, Dept. Paediatric Laboratory Medicine (DPLM), 555 University Ave, Toronto, ON M5G 1X8, Canada