Download Leukaemia Section i(6)(p10) Atlas of Genetics and Cytogenetics in Oncology and Haematology

Atlas of Genetics and Cytogenetics
in Oncology and Haematology
OPEN ACCESS JOURNAL AT INIST-CNRS
Leukaemia Section
Mini Review
i(6)(p10)
Marta Susana Gallego
Laboratorio de Citogenetica - Servicio de Genetica - Hospital de Pediatria "Prof Dr JPGarrahan", Buenos
Aires, Argentina (MSG)
Published in Atlas Database: June 2008
Online updated version : http://AtlasGeneticsOncology.org/Anomalies/i6p10ID1053.html
DOI: 10.4267/2042/44495
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
Epidemiology
Identity
Isochromosomes are a nonrandom chromosomal
anomaly in ALL. The incidence of i(6)(p10) in ALL is
0.07%. Only sixteen cases have been reported in ALL
and only one in immunoblastic lymphoma. All the
patients, except for one adult,
were children with a median age of 5 years; sex ratio:
12M/5F.
Clinics
The clinical characteristics are virtually unknown.
Prognosis
Remains to be determined. The median survival of the
reported cases varies from 7 to 40 months.
Genetics
Partial GTG banded karyotype showing i(6)(p10). Courtesy of
Cytogenetics Laboratory, Garrahan Pediatrics Hospital, Buenos
Aires, Argentina.Clinics and pathology.
Note
It has been suggested that a central part of the short arm
of chromosome 6p harbours one or more oncogenes
directly involved in tumour progression. On the other
hand, despite accumulating evidence those deletions of
chromosomal bands 6q16-q21 are a critical event in
ALL, no suppressor genes have been identified in this
region. Recently, it has been described that a minimal
deleted interval in 6q21 encompasses the FOXO3A,
PRDM1 and HACE1 candidate genes.
Disease
Acute lymphoblastic leukemia (ALL)
Phenotype/cell stem origin
B-cell precursor (pro-B,
exceptionally T ALL.
common,
pre-B)
and
Etiology
It has been suggested that, although the
isochromosomes are rarely the sole abnormality in the
majority of cases, they do occur early in the leukemic
process.
Martineau
et
al.
proposed
that
isochromosomes are mechanical indicators of genetic
events central to the etiology of the leukemia.
Atlas Genet Cytogenet Oncol Haematol. 2009; 13(6)
Cytogenetics
Note
The isochromosome 6p was found in the stemline in 12
cases and in a sideline in 5 cases. It was associated with
434
i(6)(p10)
Gallego MS
Isochromosomes in childhood acute lymphoblastic leukemia: a
collaborative study of 83 cases. Blood. 1992 May
1;79(9):2384-91
pseudo, hyper and hypodiploidies and high ploidies. It
occured more frequently at diagnosis than at relapse.
Cytogenetics molecular
Nylund SJ, Ruutu T, Saarinen U, Knuutila S. Metaphase
fluorescence in situ hybridization (FISH) in the follow-up of 60
patients with haemopoietic malignancies. Br J Haematol. 1994
Dec;88(4):778-83
Comparative genomic hybridisation studies have
detected copy-number increases affecting chromosome
6p in several types of cancer.
Cavé H, Gérard B, Martin E, Guidal C, Devaux I, Weissenbach
J, Elion J, Vilmer E, Grandchamp B. Loss of heterozygosity in
the chromosomal region 12p12-13 is very common in
childhood acute lymphoblastic leukemia and permits the
precise localization of a tumor-suppressor gene distinct from
p27KIP1. Blood. 1995 Nov 15;86(10):3869-75
Additional anomalies
The isochromosome 6p was not observed as a sole
anomaly. The majority of cases are part of a complex
karyotype and some cases occur with established
abnormalities such as der(19)t(1;19), t(12;21)(p13;q22)
and t(14;18)(q32;q21).
Chucrallah AE, Stass SA, Huh YO, Albitar M, Kantarjian HM.
Adult acute lymphoblastic leukemia at relapse. Cytogenetic,
immunophenotypic, and molecular changes. Cancer. 1995 Sep
15;76(6):985-91
Genes involved and proteins
Scaravaglio P, Saglio G, Geuna M, Palestro G, Guglielmelli T,
Rege-Cambrin G. Isochromosome 6p and deletion of 6q
characterize two related cytogenetic clones in a patient with
immunoblastic lymphoma. Cancer Genet Cytogenet. 1995
Jun;81(2):179-81
Note
Not yet defined.
Result of the chromosomal
anomaly
Martineau M, Clark R, Farrell DM, Hawkins JM, Moorman AV,
Secker-Walker LM. Isochromosomes in acute lymphoblastic
leukaemia: i(21q) is a significant finding. Genes Chromosomes
Cancer. 1996 Sep;17(1):21-30
Hybrid gene
Gutiérrez-Angulo M, González-García JR, Meza-Espinoza JP,
Picos-Cárdenas VJ, Esparza-Flores MA, López-Guido B,
Rivera H. Increased expression of AML1-a and acquired
chromosomal abnormalities in childhood acute lymphoblastic
leukemia. Hematol Oncol. 2004 Sep;22(3):85-90
Note
As a result of the formation of the isochromosome, the
structural abnormality results in monosomy for the
genes on the long arm, and trisomy for the genes in the
short arm. It is not known whether the overexpression
of a proto-oncogene or the deletion of a tumoursuppressor gene from the isochromosome contributes to
development of proliferation of leukaemia.
Kovacs BZ, Niggli FK, Betts DR. Aberrations involving 13q12
approximately q14 are frequent secondary events in childhood
acute lymphoblastic leukemia. Cancer Genet Cytogenet. 2004
Jun;151(2):157-61
Kaneko Y, Rowley JD, Variakojis D, Chilcote RR, Check I,
Sakurai M. Correlation of karyotype with clinical features in
acute
lymphoblastic
leukemia.
Cancer
Res.
1982
Jul;42(7):2918-29
Pérez-Vera P, Montero-Ruiz O, Frías S, Ulloa-Avilés V,
Cárdenas-Cardós R, Paredes-Aguilera R, Rivera-Luna R,
Carnevale A. Detection of ETV6 and RUNX1 gene
rearrangements using fluorescence in situ hybridization in
Mexican patients with acute lymphoblastic leukemia:
experience at a single institution. Cancer Genet Cytogenet.
2005 Oct 15;162(2):140-5
Prigogina EL, Puchkova GP, Mayakova SA. Nonrandom
chromosomal abnormalities in acute lymphoblastic leukemia of
childhood. Cancer Genet Cytogenet. 1988 Jun;32(2):183-203
Santos GC, Zielenska M, Prasad M, Squire JA. Chromosome
6p amplification and cancer progression. J Clin Pathol. 2007
Jan;60(1):1-7
Uckun FM, Gajl-Peczalska KJ, Provisor AJ, Heerema NA.
Immunophenotype-karyotype associations in human acute
lymphoblastic leukemia. Blood. 1989 Jan;73(1):271-80
Thelander EF, Ichimura K, Corcoran M, Barbany G, Nordgren
A, Heyman M, Berglund M, Mungall A, Rosenquist R, Collins
VP, Grandér D, Larsson C, Lagercrantz S. Characterization of
6q deletions in mature B cell lymphomas and childhood acute
lymphoblastic leukemia. Leuk Lymphoma. 2008 Mar;49(3):47787
References
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Head D, Behm F, Crist WM, Link M, Borowitz M. Morphologic,
immunologic and cytogenetic studies in children with acute
lymphoblastic leukemia at diagnosis and relapse: a Pediatric
Oncology Group study. Leukemia. 1992 May;6(5):357-62
This article should be referenced as such:
Gallego MS. i(6)(p10). Atlas Genet Cytogenet Oncol Haematol.
2009; 13(6):434-435.
Pui CH, Carroll AJ, Raimondi SC, Schell MJ, Head DR,
Shuster JJ, Crist WM, Borowitz MJ, Link MP, Behm FG.
Atlas Genet Cytogenet Oncol Haematol. 2009; 13(6)
435