Atlas of Genetics and Cytogenetics in Oncology and Haematology


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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

+8 or trisomy 8

Clinics and Pathology

Disease Chronic myelogenous leukaemia (CML)
Epidemiology +8 is one of the major anomalies additional to the t(9;22), with i(17q), + der(22), before +19; found as a unique additional anomaly in 10%, with other in 25% of CML cases with clonal evolution; these additional anomalies may be present at the diagnosis of CML (in 10%, possibly with unfavourable significance), or may appear during course of the disease, they do not indicate the imminence of a blast crisis, although they also frequently emerge at the time of acute transformation; +8 is more often found in the myeloid than in the lymphoid blast crisis.
Prognosis +8 has apparently no prognostic significance in CML; +8 may arise after interferon and/or imatinib treatment. It's significance is unknown.

Disease Other chronic myeloproliferative diseases: polycytemia vera (PV), and idiopathic myelofibrosis (but not found in essential thrombocythemia).
Epidemiology +8 is found in 20% of PV cases with an abnormal karyotype, mostly as the sole anomaly, may be accompanied with +9 (abnormal karyotypes in PV occur mainly with evolution, but the appearance of a clonal anomaly does not indicate progression of the disease); +8 is found in 10% of myelofibrosis cases with chromosome anomalies, sometimes with +9.
Prognosis No prognostic significance

Disease Myelodysplastic syndromes (MDS): refractory anaemia (RA), refractory anaemia with ring sideroblasts (RARS), refractory anaemia with excess of blasts in transformation (RAEBT), chronic myelomonocytic leukaemia (CMML).
Note The present (unpublished) review of about 250 MDS cases with +8 is a review of literature cases and may therefore be biased, although the percentages herein given are in accordance with those of large series.
Epidemiology +8 is found in 15-20% of MDS; 5-10% of MDS with +8 are treatment-related MDS; +8 is present in each FAB subgroup: up to 25-30% of RARS cases have +8; 15-20% of other subgroups have +8
+8 is : the sole anomaly in 55-65%, found with simple karyopypic changes in 20%, and part of a complex karyotype in the remaining 25% of cases
Altogether, sex ratio is significantly unbalanced, near 1.5M/1F (1.8/1 in cases RAEBT and CMML, 1/1 in RA or RARS)
- 15% of +8/MDS are found with -5/del(5q), often in complex karyotypes
- 4% of +8/MDS are found with t(1;7)(q10;p10)(and 20% of t(1;7)/MDS-AML also associate +8)
- 4% as well are found with del(20q), mainly in simple karyotypes
- +8 is strickingly found in independant subclones, with other subclones carrying other anomalies, in particular del(5q) or t(1;7) (e.g. : 46, XY, del(5q)/47, XY, +8).
Prognosis Progression from MDS towards AML would occur in about half cases of +8 solely. Median survival in these cases would be about 1.5-2 yrs

Disease Acute myeloid leukaemias (AML)
Note The present (unpublished) review of more than 500 AML cases with +8 is a review of literature cases and may therefore be biased, although the percentages herein given are in accordance with those of large series; we also add 39 unpublished t(11;19) to 101 published cases.
Epidemiology +8 is found in 10-15% of AML; 10% of AML with +8 are treatment-related AML; +8 is present in each FAB subgroup (from M1 to M7) in a grossly equivalent percentage (but in M3, where the percentage is lower (2% as the sole anomaly, 10% altogether), and in M5 where the percentage is higher (10% as the sole anomaly, 20-30% altogether) ), in contrast to what has been previously claimed; cases may present with a preceeding myelodysplasia. +8 is not more frequent in treatment related leukaemias.
+8 is : the sole anomaly in 40%, found with simple karyopypic changes in 35%, and part of a complex karyotype in the remaining 25% of cases. Altogether, sex ratio is 1.2/1 (1.6/1 in cases with a complex karyotype, 1/1 otherwise)
- 5-10% of +8/AML are found with -5/del(5q)and/or -7/del(7q), often associated, and nearly always in complex karyotypes.
- 5-10% also are found in t(15;17)/M3 cases, mostly as a single additional anomaly, while 1/3 of t(15;17) are accompanied with +8
- 5-10% are found with inv(16), mainly in simple karyotypes (and 15% of inv(16) cases also carry +8)
- 5% are associated with +21, often parts of a complex karyotype
- 5% also are found in 11q23 AML, mostly in t(9;11)(p22;q23) cases (20% of t(9;11) carry +8), while 15% of t(11;19)(q23;p13.3)/AML or ALL (91 cases, 25 unpublished), 10% of t(6;11)(q27;q23)/AML,t(10;11)(p12;q23)/AML, and t(11;19)(q23;p13.1)/AML (49 cases, 14 unpublished) as well, and only 3% of t(4;11)(q21;q23)/ALL, have an additional 8 chromosome; +8 is also frequently associated to a t(1;11)(p32;q23)
- less than 5% are found with t(8;21)(q21;q21) often in simple karyotypes, and 10% of t(8;21) associate +8
- less than 5% also are associated with t(9;22)(q34;q11)/AML, mostly in complex karyotypes.
- 2% are associated with +9, either in simple or in complex karyotypes.
- 1% of +8/AML are found with t(1;7)(q10;p10), but as far as 20% of t(1;7) also associate +8
- 15% of Down syndrome patients with MDS/AML have +8 in their leukaemic cells.
+8 is also found in 15% of t(9;22)(q34;q11) and 25% of t(7;12)(q36;p13) cases.
Clinics From 2 studies on AML in adults with +8 solely: no specific FAB subgroup; median age was 60 yrs (vs 50 yrs in cases of +8 accompanying t(8;21), t(15;17) or inv(16)); no gross organomegaly; moderate WBC.
Prognosis Prognosis of AML in adults with +8 solely: complete remission in 60-70% (vs 90% in cases accompanying t(8;21), t(15;17) or inv(16)); median survival was 13 mths in one study, 20 mths in another, around 1 year in most; taking all +8 cases, solely or not, median survival would be of about a year; +8 does not seem to alter the relatively good prognosis of t(8;21), t(15;17) or inv(16), while the (numerous) cases with a complex karyotype exhibit a poor outcome; age is an adverse feature. +8 can be associated with intermediate or poor prognosis.

Disease Acute lymphocytic leukaemia (ALL)
Phenotype / cell stem origin +8 is more often found in B-cell than in T-cell cases.
Epidemiology - +8 is a rare anomaly in lymphoid malignancies (90% of +8 occur in myeloid malignancies); found in about 5% of ALL.
- rarely found as a sole anomaly (5-10%), may be part of hyperploid karyotypes (>50 chromosomes mainly) without structural anomalies (20% of cases), mostly found in complex karyotypes with structural anomalies (2/3 of cases), these complex karyotypes being often hyperploid as well
- sex ratio : 1.5/1
- accompany (mostly in complex karyotypes) : t(9;22)(q34;q11)/ALL, t(4;11) (see above) and other 11q23, del(6q), t(1;19)(q23;p13), dic(9;12) and other known primary anomalies.

Disease Non-Hodgkin lymphomas
Epidemiology +8 is exceptional; has been found associated with t(14;18)(q32; q21), t(8;14)(q24;q32), and other known or unknown anomalies.

Disease Chronic lymphoproliferative diseases
Epidemiology Very rare anomaly (to be noted that +8 is exceptional in T-prolymphocytic leukaemia, in contrast with the freqency of i(8q), which occurs by completely different mechanisms, but gives, for parts, very similar genetic imbalances).

Disease Solid tumours

Desmoid fibromatosisand Dupuytren's contracture; +8 is found, mostly as the sole anomaly, in 25% of cases.
Clear cell sarcoma with t(12;22)(p11;p11) : +8 is found in 55% of cases of clear cell sarcoma.
Ewing tumors with t(11;22)(q24;q12) : +8 is found in 35% of cases of Ewing tumors.
Myxoid liposarcoma with t(12;16)(q13;p11) : +8 is found in 15% of cases of myxoid liposarcoma.
Synovial sarcoma with t(X;18)(p11;q11) : +8 is found in 10% of cases of synovial sarcoma.
Hepatoblastoma : +8 is found (with other anomalies) in 35% of cases of hepatoblastoma.
Wilms tumor : +8 is found (with other anomalies) in 25% of cases of cases of Wilms tumor. ... and others.

Genetics

Genes (possibly) involved are unknown. The leukaemias with +8 appear to be a heterogenous group, with different clinical and cytologic presentations, and different expression profiles as well.
+8 is likely to be a secondary event, even in the cases where no known primary anomaly is associated to the +8, and also even in the trisomy 8 solely cases, where cryptic events -such as cryptic translocations or deletions, or mutations- remain to be found as primary events.
Imprinting data gave no particular results.
Constitutional trisomy 8 patients have an increased risk of developping a leukaemia

External links

Other database+8 or trisomy 8 Mitelman database (CGAP - NCBI)

To be noted

karyotypes with +8 may be misinterpreted with a possible overlooked constitutional trisomy 8, a syndrome associating mild to moderate mental delay and (sometimes mild as well) bone anomalies; furthermore constitutional trisomy 8 has been said to be at increased rirk of cancers, haematological malignancies in particular.

Other genes implicated (Data extracted from papers in the Atlas)

Genes ABL1 ASXL1 BAALC BCR CREBBP FGFR1 PML RARA

Bibliography

MDS and AML with trisomy 8 as the sole chromosome aberration show different sex ratios and prognostic profiles: a study of 115 published cases.
Pedersen B
American journal of hematology. 1997 ; 56 (4) : 224-229.
PMID 9395183
 
Constitutional trisomy 8 as first mutation in multistep carcinogenesis: clinical, cytogenetic, and molecular data on three cases.
Seghezzi L, Maserati E, Minelli A, Dellavecchia C, Addis P, Locatelli F, Angioni A, Balloni P, Miano C, Cavalli P, Danesino C, Pasquali F
Genes, chromosomes & cancer. 1996 ; 17 (2) : 94-101.
PMID 8913726
 
The significance of trisomy 8 in de novo acute myeloid leukaemia: the accompanying chromosome aberrations determine the prognosis. German AML Cooperative Study Group.
Schoch C, Haase D, Fonatsch C, Haferlach T, Lffler H, Schlegelberger B, Hossfeld DK, Becher R, Sauerland MC, Heinecke A, Wrmann B, Bchner T, Hiddemann W
British journal of haematology. 1997 ; 99 (3) : 605-611.
PMID 9401073
 
Patients with isolated trisomy 8 in acute myeloid leukemia are not cured with cytarabine-based chemotherapy: results from Cancer and Leukemia Group B 8461.
Byrd JC, Lawrence D, Arthur DC, Pettenati MJ, Tantravahi R, Qumsiyeh M, Stamberg J, Davey FR, Schiffer CA, Bloomfield CD
Clinical cancer research : an official journal of the American Association for Cancer Research. 1998 ; 4 (5) : 1235-1241.
PMID 9607582
 
Trisomy 8 as the sole chromosomal aberration in acute myeloid leukemia and myelodysplastic syndromes.
Paulsson K, Johansson B
Pathologie-biologie. 2007 ; 55 (1) : 37-48.
PMID 16697122
 
Mitelman Database of Chromosome Aberrations in Cancer
Mitelman F, Johansson B and Mertens F
http..
 
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed

Contributor(s)

Written11-1998Jean Loup Huret
Genetics, Dept Medical Information, University of Poitiers; CHU Poitiers Hospital, F-86021 Poitiers, France
Updated12-2007Jean Loup Huret
Genetics, Dept Medical Information, University of Poitiers; CHU Poitiers Hospital, F-86021 Poitiers, France

Citation

This paper should be referenced as such :
Huret JL . +8 or trisomy 8. Atlas Genet Cytogenet Oncol Haematol. November 1998 .
Huret JL . +8 or trisomy 8. Atlas Genet Cytogenet Oncol Haematol. December 2007 .
URL : http://AtlasGeneticsOncology.org/Anomalies/tri8ID1017.html

The various updated versions of this paper are referenced and archived by INIST as such :
http://documents.irevues.inist.fr/bitstream/2042/37486/1/11-1998-tri8ID1017.pdf   [ Bibliographic record ]
http://documents.irevues.inist.fr/bitstream/2042/44390/1/12-2007-tri8ID1017.pdf   [ Bibliographic record ]

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indexed on : Fri Apr 18 14:12:45 CEST 2014


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