+8 or trisomy 8

2007-12-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers; CHU Poitiers Hospital, F-86021 Poitiers, France

Clinics and Pathology

Disease

Chronic myelogenous leukaemia (CML)  ,  Chronic lymphoproliferative diseases  , 
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.

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. , - 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. , - 4% of +8/MDS are found with t(1;7)(q10;p10)(and 20% of t(1;7)/MDS-AML also associate +8)
 , +8 is exceptional; has been found associated with t(14;18)(q32; q21), t(8;14)(q24;q32), and other known or unknown anomalies. , - +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). , +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.

Prognosis

+8 has apparently no prognostic significance in CML; +8 may arise after interferon and/or imatinib treatment. Its significance is unknown.

Disease

Other chronic myeloproliferative diseases: polycytemia vera (PV), and idiopathic myelofibrosis (but not found in essential thrombocythemia).

Epidemiology

- 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

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. , +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

Epidemiology

- +8 is a rare anomaly in lymphoid malignancies (90% of +8 occur in myeloid malignancies); found in about 5% of ALL.

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

Solid tumours

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.

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 stem cell origin

+8 is more often found in B-cell than in T-cell cases.

Disease

Non-Hodgkin lymphomas

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


Desmoid fibromatosis and Dupuytrens contracture; +8 is found, mostly as the sole anomaly, in 25% of cases.

Note

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.

Bibliography

Pubmed IDLast YearTitleAuthors
96075821998Patients 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 et al
166971222007Trisomy 8 as the sole chromosomal aberration in acute myeloid leukemia and myelodysplastic syndromes.Paulsson K et al
93951831997MDS 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 et al
94010731997The significance of trisomy 8 in de novo acute myeloid leukaemia: the accompanying chromosome aberrations determine the prognosis. German AML Cooperative Study Group.Schoch C et al
89137261996Constitutional trisomy 8 as first mutation in multistep carcinogenesis: clinical, cytogenetic, and molecular data on three cases.Seghezzi L et al

Summary

Atlas Image
Trisomy 8 Detection of trisomy 8 using fluorescence in situ hybridization with the Vysis CEP 8 SpectrumOrange probe specific for the alpha satellite (centromeric) region, 8p11.1-q11.1 (Abbott Molecular, US) and LSI RUNX1/RUNX1T1 probes showing extra signals in metaphase chromosomes and interphase nuclei - Courtesy Adriana Zamecnikova.

Citation

Jean-Loup Huret

+8 or trisomy 8

Atlas Genet Cytogenet Oncol Haematol. 2007-12-01

Online version: http://atlasgeneticsoncology.org/haematological/1017/+8-or-trisomy-8

Historical Card

1998-11-01 +8 or trisomy 8 by  Jean-Loup Huret 

Genetics, Dept Medical Information, University of Poitiers; CHU Poitiers Hospital, F-86021 Poitiers, France

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