+18 or trisomy 18 in lymphoproliferative disorders
2003-09-01 Daniel L Van Dyke Affiliation1.FACMG, Cytogenetics Laboratory, Mayo Clinic, USA
Clinics and Pathology
Noted
Trisomy 18 seen with other abnormalities is fairly nonspecific, having been reported in most lymphoproliferative disorders. Trisomy 18 as a sole abnormality is also nonspecific, having been reported in MDS, AML, ALL (14 cases), lymphoma (3 of 6 reported cases were follicular lymphoma), Hodgkins disease (two cases) and CLL (10 cases).
Disease
Acute lymphocytic leukemia (ALL)
Note
Trisomy 18 is common in hyperdiploid ALL with more than 50 chromosomes (15-27% of cases). The great majority of karyotypes with trisomy 18 also exhibit trisomy 4, 6, 10, and 14, either trisomy 21 or tetrasomy 21, and an extra X chromosome. More than half either have trisomy 17 or an isochromosome 17q. It is unusual to see trisomy 18 in a hyperdiploid ALL with fewer than 50 chromosomes. It is likewise unusual to find trisomy 18 associated with one of the common structural changes in ALL, such as the 1;19. However, at least two hyperdiploid ALL cases have been reported with trisomy 18 and tetrasomy 21 in which a t(12;21) was detected by FISH analysis; further research is indicated. ,
- In DLBCL, the karyotype with trisomy 18 is usually hyperdiploid with 47-52 chromosomes and with multiple chromosome rearrangements. Trisomy 3 accompanies trisomy 18 in about 30% of cases, and trisomies 7, 12, and 21 in about 10% each. About 10% have a t(14;18) or +der(18)(t(14;18), about 5% have a t(8;14), and another 10% have another 14q32 rearrangement. About 20% have a 6q rearrangement or an i(6)(p10) that results in loss of 6q, and about 20% have an extra X chromosome, many of which are structurally abnormal.
- In FL, the general cytogenetic pattern of cases with trisomy 18 is similar to that of DLBCL. The principle difference is that about 75% of cases exhibit a t(14;18) or an add(14)(q32), and association of trisomy 18 and a t(8;14) is very uncommon.
- Trisomy 18 is a recurrent finding in MZBCL, seen in 39% of cases in one study. About a third of marginal zone lymphomas with trisomy 3 also exhibit trisomy 18.
- About 10% of peripheral T-cell lymphomas exhibit trisomy 18, and then usually as part of a fairly complex karyotype.
Epidemiology
Of 14 reported ALL cases with trisomy 18 as the sole cytogenetic abnormality, nine were reported from India. Is there an environmental component to this unusual distribution of cases?
Prognosis
The prognosis appears to be neutral to favorable in a karyotype with >51 chromosomes that includes trisomy 18. There is some evidence of an unfavorable prognosis if the karyotype is isolate trisomy 18.
Disease
Chronic lymphocytic leukemia
Note
Trisomy 18 is very uncommon in CLL. When observed, it usually presents as the sole abnormality, or with a karyotype of 49, +12, +18, +19. The karyotype is occasionally more complex.
Prognosis
No correlation between trisomy 18 and prognosis.
Disease
Non-Hodgkins lymphoma
Note
Trisomy 18 is observed in 15-33% of lymphomas, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and marginal zone B-cell lymphoma (MZBCL). Trisomy 18 may be less frequent in other NHL sub-types.
Cytology
The Hodgkins disease cases with trisomy 18 have included both the mixed cellularity and the nodular sclerosis types.
Epidemiology
Of CLL cases reported with trisomy 18, about 15% exhibited apparently independent cytogenetically abnormal cell populations, with isolated trisomy 18 as one of two, three, or more clones. The clinical significance of these clones is not understood.
Note
Trisomy 18 is strongly associated with a t(14;18) or at least a 14q32 abnormality, and may represent a variant of the +der(18)t(14;18), which duplicates the segment 18pter-18q21. Trisomy 18 is rarely observed as the primary cytogenetic change in NHL.
Phenotype stem cell origin
Overexpression of BCL2 has been reported in trisomy 18 without t(14;18). CGH studies suggest duplication 18q (which would include trisomy 18) tend to occur early in the cytogenetic evolution. In FL, 18q gains were most common in young males and occurred with similar frequency in FL with and without t(14;18).
Prognosis
Trisomy 18 as a secondary abnormality in NHL has no significant influence on tumor grade or overall survival.
Genes Involved and Proteins
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 10914938 | 2000 | Cytogenetic and FISH studies of a single center consecutive series of 152 childhood acute lymphoblastic leukemias. | Andreasson P et al |
| 8642049 | 1996 | Clinical implications of cytogenetic classification in adult acute lymphoblastic leukaemia patients. | Ankathil R et al |
| 9115968 | 1997 | Cytogenetic analysis of 280 patients with multiple myeloma and related disorders: primary breakpoints and clinical correlations. | Calasanz MJ et al |
| 8547655 | 1996 | Marginal zone B-cell lymphomas of different sites share similar cytogenetic and morphologic features. | Dierlamm J et al |
| 1596572 | 1992 | Trisomy of leukemic cell chromosomes 4 and 10 identifies children with B-progenitor cell acute lymphoblastic leukemia with a very low risk of treatment failure: a Pediatric Oncology Group study. | Harris MB et al |
| 10784628 | 2000 | Prognostic impact of trisomies of chromosomes 10, 17, and 5 among children with acute lymphoblastic leukemia and high hyperdiploidy (> 50 chromosomes). | Heerema NA et al |
| 11156736 | 2000 | Importance of using comparative genomic hybridization to improve detection of chromosomal changes in childhood acute lymphoblastic leukemia. | Jarosová M et al |
| 10089896 | 1999 | Prognostic implications of cytogenetic aberrations in diffuse large B-cell lymphomas. | Jerkeman M et al |
| 8266916 | 1993 | Phenotypic and genotypic characterization of Hodgkin's disease. | Koduru PR et al |
| 11343778 | 2001 | Chromosomal analyses of 52 cases of follicular lymphoma with t(14;18), including blastic/blastoid variant. | Mohamed AN et al |
| 8167342 | 1994 | Clinical and morphologic features of B-cell small lymphocytic lymphoma with del(6)(q21q23). | Offit K et al |
| 7627933 | 1995 | Cytogenetic findings in 200 patients with multiple myeloma. | Sawyer JR et al |
| 9639426 | 1998 | Chromosomal analysis in multiple myeloma: cytogenetic evidence of two different diseases. | Smadja NV et al |
| 3297304 | 1987 | Chromosomal abnormalities in indolent lymphoma. | Speaks SL et al |
| 8049424 | 1994 | Prognostic value of chromosomal abnormalities in follicular lymphoma. | Tilly H et al |
| 12454108 | 2002 | Clinicopathologic correlations of genomic gains and losses in follicular lymphoma. | Viardot A et al |
| 7803794 | 1995 | Sequential analysis of 43 patients with non-Hodgkin's lymphoma: clinical correlations with cytogenetic, histologic, immunophenotyping, and molecular studies. | Whang-Peng J et al |
| 11120335 | 2000 | Follicular lymphoma with trisomy 18 and over-expression of BCL2 in the absence of t(14;18)(q32;q21). | Wong KF et al |
Citation
Daniel L Van Dyke
+18 or trisomy 18 in lymphoproliferative disorders
Atlas Genet Cytogenet Oncol Haematol. 2003-09-01
Online version: http://atlasgeneticsoncology.org/haematological/2030/+18-or-trisomy-18-in-lymphoproliferative-disorders
