**+8 or trisomy 8**

**2007-12-01**Jean-Loup Huret Affiliation

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.

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.

, - 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

, 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 ID | Last Year | Title | Authors |
---|---|---|---|

9607582 | 1998 | 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 et al |

16697122 | 2007 | Trisomy 8 as the sole chromosomal aberration in acute myeloid leukemia and myelodysplastic syndromes. | Paulsson K et al |

9395183 | 1997 | 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 et al |

9401073 | 1997 | 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 et al |

8913726 | 1996 | Constitutional trisomy 8 as first mutation in multistep carcinogenesis: clinical, cytogenetic, and molecular data on three cases. | Seghezzi L et al |

### Summary

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
Affiliation

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