-7/del(7q) in adults

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home Genes Leukemias Solid Tumors Cancer-Prone Deep Insight Case Reports Journals Portal Teaching

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

-7/del(7q) in adults

Written	1999-06	François Desangles
		Laboratoire de Biologie, Hopital du Val de Grace, 75230 Paris, France

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS

ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS

ICD-Morpho 9920/3 Therapy-related myeloid neoplasms

ICD-Morpho 9989/3 Myelodysplastic syndrome, unclassifiable

Atlas_Id 1093

Note -7/del(7q) in childhood blood malignancies exhibits a specific pattern of pathogenesis; chromosome 7 anomalies are not rare in acute lymphocytic leukaemia (ALL); they occur in balanced translocations involving 7p15 or 7q34 in T lineage and 7q22 or 7q32 in B proliferations; monosomy 7 is present in 5 to 6 % of ALL, most often as a secondary anomaly of the t(9;22); the association t(9;22), -7 is present in 16 % of the Ph1+ ALL, i.e. in 3% of ALL as a whole; we will hereunder focuse on -7/del(7q) in adult myeloproliferations

del(7q) Figure 1: Partial karyotypes with 7q deletions (A). Fluorescence in situ hybridization with Vysis D7S486 (7q31)/CEP 7 probe (Abbott moleculars, US) showing 2 green and 2 red signals on normal and one red signal in abnormal metaphases indicating 7q deletion of various sizes (C-H) – Courtesy Adriana Zamecnikova. Figure 2: del(7q) G- banding - Courtesy Jean-Luc Lai and Alain Vanderhaegen; Hybridization with Vysis D7S486 (7q31)/CEP 7 probe (Abbott moleculars, US) showing 1 green and 1 red signal confirming monosomy 7on metaphase and interphase cells – Courtesy Adriana Zamecnikova.

Clinics and Pathology

Disease myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML); they may occur de novo, or be secondary to an exposure to chemical mutagens or to chemotherapy treatments with alkylating agents; may probably also be secondary to immunosuppressive therapy for severe aplastic anemia

Phenotype / cell stem origin
MDS cases : found in 30% of RAEB/RAEB-T, 20% of CMML, and only 5% of RA with an abnormal karyotype;
AML most often M4 or M6 ;
Monosomy 7 and these deletions does not seem a specific feature of the dysplastic clone in the MDS, they are secondary events contributing to the leucogenesis

Epidemiology -7 is the most frequent abnormality in secondary myeloid disorders, found in 51% of the cases in a series of 246 cases, while del(7q) was found in 7%, and a partial monosomy 7 as a result of an unbalanced translocation in 8% of cases; in contrast, -7/del(7q) is found in 10% of de novo myeloid disorders; the sex ratio is 1.5 male for 1 female; the proportion of adults with a -7 myeloid disorder grows dramatically after 60 years

Clinics characterized by infectious susceptibility, quick aggravation, and treatment resistance

Prognosis monosomy 7 is classified as a poor prognostic criterium by the International Prognostic Scoring System; the actuarial relapse rate at one year is 82 %, and the 7-yr actuarial event-free survival is 6 %; after an allogeneic bone marrow transplantation, -7 is predictive of an unfavorable outcome

Cytogenetics

Cytogenetics Morphological deletion (7q) is always interstitial; cluster of breakpoints in 7q11 to 7q36, is a with two common minimal zones in q22 and in q32-34

Cytogenetics Molecular using loss of heterogygocity (LOH) studies and YAC libraries, a 2 to 3 Mb segment in 7q22 has been designated as the proximal common deleted area; the 7q33-34 zone is the consensual area for the distal deletion; LOH studies suggest that a specific mechanism, such as mitotic recombination in bone marrow stem cell leading to homozygosity in both granulocytes and lymphocytes, may be implicated

Additional anomalies -5/del(5q), found in 40 to 60 % of the secondary MDS cases; trisomy 8

Variants the balanced translocation t(1;7)(q10;p10), and many unbalanced translocation, having for consequence a partial monosomy 7 of the 7q22 to 7q34 bands may, in a way, be considered as variants

Genes involved and Proteins

Note -7/del(7q) is not only frequent in secondary MDS or AML, but also in leukemias occurring in individuals with constitutional syndromes including predisposition to myeloid disorders; these findings suggest the presence of a putative myeloid leukemia suppressor gene in the commonly deleted genomic segment 7q22 and even multiple genes in 7q22 -31.1 that are playing a role in leukemogenesis;
candidate genes are :
ASNS (asparagine synthetase gene) in 7q21.3-q22.1;
ACHE (acetyl cholinesterase),
EPO (erythropoietin),
PLANH1 (plasminogen activator inhibitor 1) in 7q22; and
MET in 7q31.2-31.3

Bibliography

Cytokine modulation of the susceptibility of acute T-lymphoblastic leukemia cell lines to LAK activity.

Cesano A, Clark SC, Santoli D

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1993 ; 7 (3) : 404-409.

PMID 8445946

Molecular cytogenetic delineation of deletions and translocations involving chromosome band 7q22 in myeloid leukemias.

Fischer K, Fröhling S, Scherer SW, McAllister Brown J, Scholl C, Stilgenbauer S, Tsui LC, Lichter P, Döhner H

Blood. 1997 ; 89 (6) : 2036-2041.

PMID 9058725

Correlation of occupation and karyotype in adults with acute nonlymphocytic leukemia.

Golomb HM, Alimena G, Rowley JD, Vardiman JW, Testa JR, Sovik C

Blood. 1982 ; 60 (2) : 404-411.

PMID 7093525

Neutrophil dysplasia is not a specific feature of the abnormal chromosomal clone in myelodysplastic syndromes.

Hast R, Eriksson M, Widell S, Arvidsson I, Bemell P

Leukemia research. 1999 ; 23 (6) : 579-584.

PMID 10374851

Cytogenetics of secondary myelodysplasia (sMDS) and acute nonlymphocytic leukemia (sAML).

Johansson B, Mertens F, Heim S, Kristoffersson U, Mitelman F

European journal of haematology. 1991 ; 47 (1) : 17-27.

PMID 1868912

Monosomy 7 and 7q--associated with myeloid malignancy.

Johnson E, Cotter FE

Blood reviews. 1997 ; 11 (1) : 46-55.

PMID 9218106

Molecular definition of a narrow interval at 7q22.1 associated with myelodysplasia.

Johnson EJ, Scherer SW, Osborne L, Tsui LC, Oscier D, Mould S, Cotter FE

Blood. 1996 ; 87 (9) : 3579-3586.

PMID 8611680

Evidence for two molecular steps in the pathogenesis of myeloid disorders associated with deletion of chromosome 7 long arm.

Kiuru-Kuhlefelt S, Kristo P, Ruutu T, Knuutila S, Kere J

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1997 ; 11 (12) : 2097-2104.

PMID 9447826

Allelotyping of acute myelogenous leukemia: loss of heterozygosity at 7q31.1 (D7S486) and q33-34 (D7S498, D7S505).

Koike M, Tasaka T, Spira S, Tsuruoka N, Koeffler HP

Leukemia research. 1999 ; 23 (3) : 307-310.

PMID 10071086

Cytogenetic and molecular delineation of a region of chromosome 7 commonly deleted in malignant myeloid diseases.

Le Beau MM, Espinosa R 3rd, Davis EM, Eisenbart JD, Larson RA, Green ED

Blood. 1996 ; 88 (6) : 1930-1935.

PMID 8822909

Molecular anatomy of chromosome 7q deletions in myeloid neoplasms: evidence for multiple critical loci.

Liang H, Fairman J, Claxton DF, Nowell PC, Green ED, Nagarajan L

Proceedings of the National Academy of Sciences of the United States of America. 1998 ; 95 (7) : 3781-3785.

PMID 9520444

Childhood monosomy 7: epidemiology, biology, and mechanistic implications.

Luna-Fineman S, Shannon KM, Lange BJ

Blood. 1995 ; 85 (8) : 1985-1999.

PMID 7718870

Cytogenetic abnormalities in primary myelodysplastic syndrome are highly predictive of outcome after allogeneic bone marrow transplantation.

Nevill TJ, Fung HC, Shepherd JD, Horsman DE, Nantel SH, Klingemann HG, Forrest DL, Toze CL, Sutherland HJ, Hogge DE, Naiman SC, Le A, Brockington DA, Barnett MJ

Blood. 1998 ; 92 (6) : 1910-1917.

PMID 9731047

Deletion of the acetylcholinesterase locus at 7q22 associated with myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML).

Stephenson J, Czepulkowski B, Hirst W, Mufti GJ

Leukemia research. 1996 ; 20 (3) : 235-241.

PMID 8637218

Cytogenetic clonality analysis in myelodysplastic syndrome: monosomy 7 can be demonstrated in the myeloid and in the lymphoid lineage.

van Lom K, Hagemeijer A, Smit E, Hählen K, Groeneveld K, Löwenberg B

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1995 ; 9 (11) : 1818-1821.

PMID 7475268

Citation

This paper should be referenced as such :

Desangles, F

-7/del(7q) in adults

Atlas Genet Cytogenet Oncol Haematol. 1999;3(3):139-140.

Free journal version : [ pdf ] [ DOI ]

On line version : http://AtlasGeneticsOncology.org/Anomalies/del7qID1093.html

Translocations implicated (Data extracted from papers in the Atlas)

del(7q) in adults

External links

Mitelman database del(7q) [Case List] del(7q) [Transloc-MCList] in [Fusion-MCList]
arrayMap (UZH-SIB Zurich) Topo ( C42) Morph ( 9861/3) - [auto + random 100 samples .. if exist ] [tabulated segments]

arrayMap (UZH-SIB Zurich) Topo ( C42) Morph ( 9920/3) - [auto + random 100 samples .. if exist ] [tabulated segments]

arrayMap (UZH-SIB Zurich) Topo ( C42) Morph ( 9989/3) - [auto + random 100 samples .. if exist ] [tabulated segments]

REVIEW articles automatic search in PubMed

Last year articles automatic search in PubMed

All articles automatic search in PubMed

Home Genes Leukemias Solid Tumors Cancer-Prone Deep Insight Case Reports Journals Portal Teaching

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.

ICD-Topo	C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
ICD-Morpho	9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
ICD-Morpho	9920/3 Therapy-related myeloid neoplasms
ICD-Morpho	9989/3 Myelodysplastic syndrome, unclassifiable
Atlas_Id	1093
Note	-7/del(7q) in childhood blood malignancies exhibits a specific pattern of pathogenesis; chromosome 7 anomalies are not rare in acute lymphocytic leukaemia (ALL); they occur in balanced translocations involving 7p15 or 7q34 in T lineage and 7q22 or 7q32 in B proliferations; monosomy 7 is present in 5 to 6 % of ALL, most often as a secondary anomaly of the t(9;22); the association t(9;22), -7 is present in 16 % of the Ph1+ ALL, i.e. in 3% of ALL as a whole; we will hereunder focuse on -7/del(7q) in adult myeloproliferations


	del(7q) Figure 1: Partial karyotypes with 7q deletions (A). Fluorescence in situ hybridization with Vysis D7S486 (7q31)/CEP 7 probe (Abbott moleculars, US) showing 2 green and 2 red signals on normal and one red signal in abnormal metaphases indicating 7q deletion of various sizes (C-H) – Courtesy Adriana Zamecnikova. Figure 2: del(7q) G- banding - Courtesy Jean-Luc Lai and Alain Vanderhaegen; Hybridization with Vysis D7S486 (7q31)/CEP 7 probe (Abbott moleculars, US) showing 1 green and 1 red signal confirming monosomy 7on metaphase and interphase cells – Courtesy Adriana Zamecnikova.

Disease	myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML); they may occur de novo, or be secondary to an exposure to chemical mutagens or to chemotherapy treatments with alkylating agents; may probably also be secondary to immunosuppressive therapy for severe aplastic anemia
Phenotype / cell stem origin	MDS cases : found in 30% of RAEB/RAEB-T, 20% of CMML, and only 5% of RA with an abnormal karyotype; AML most often M4 or M6 ; Monosomy 7 and these deletions does not seem a specific feature of the dysplastic clone in the MDS, they are secondary events contributing to the leucogenesis
Epidemiology	-7 is the most frequent abnormality in secondary myeloid disorders, found in 51% of the cases in a series of 246 cases, while del(7q) was found in 7%, and a partial monosomy 7 as a result of an unbalanced translocation in 8% of cases; in contrast, -7/del(7q) is found in 10% of de novo myeloid disorders; the sex ratio is 1.5 male for 1 female; the proportion of adults with a -7 myeloid disorder grows dramatically after 60 years
Clinics	characterized by infectious susceptibility, quick aggravation, and treatment resistance
Prognosis	monosomy 7 is classified as a poor prognostic criterium by the International Prognostic Scoring System; the actuarial relapse rate at one year is 82 %, and the 7-yr actuarial event-free survival is 6 %; after an allogeneic bone marrow transplantation, -7 is predictive of an unfavorable outcome

Cytogenetics Morphological	deletion (7q) is always interstitial; cluster of breakpoints in 7q11 to 7q36, is a with two common minimal zones in q22 and in q32-34
Cytogenetics Molecular	using loss of heterogygocity (LOH) studies and YAC libraries, a 2 to 3 Mb segment in 7q22 has been designated as the proximal common deleted area; the 7q33-34 zone is the consensual area for the distal deletion; LOH studies suggest that a specific mechanism, such as mitotic recombination in bone marrow stem cell leading to homozygosity in both granulocytes and lymphocytes, may be implicated
Additional anomalies	-5/del(5q), found in 40 to 60 % of the secondary MDS cases; trisomy 8
Variants	the balanced translocation t(1;7)(q10;p10), and many unbalanced translocation, having for consequence a partial monosomy 7 of the 7q22 to 7q34 bands may, in a way, be considered as variants

Mitelman database	del(7q) [Case List] del(7q) [Transloc-MCList] in [Fusion-MCList]
arrayMap (UZH-SIB Zurich)	Topo ( C42) Morph ( 9861/3) - [auto + random 100 samples .. if exist ] [tabulated segments]
arrayMap (UZH-SIB Zurich)	Topo ( C42) Morph ( 9920/3) - [auto + random 100 samples .. if exist ] [tabulated segments]
arrayMap (UZH-SIB Zurich)	Topo ( C42) Morph ( 9989/3) - [auto + random 100 samples .. if exist ] [tabulated segments]

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