| Cytogenetics Morphological | sole anomaly in 20 %; numerical and structural rearrangements of chromosomes 5 and 7 frequently associated (found in 50% in de novo cases). del(12p): due to the very heterogeneous breakpoints in 12p (assigned to all chromosome bands), no cytogenetic subgroups are defined; deletion in 12p is generally associated with a poor prognosis; however, different clinical courses are defined concerning the magnitude of 12p; a group with small deletions has a better prognosis than patients with 12p abnormalities in general and a lower tendency to additional chromosomal rearrangements; submicroscopic deletions of 12p are much more common in lymphoid than in myeloid malignancies; a minimal interstitial deletion region is described, involving ETV6 and CDKN1B genes; hemozygous deletion of CDKN1B is rare (the other wild allele never found mutated); none of the malignancies with disease specific changes displayed submicroscopic 12p deletions. dup(12)(p11.2p13) described in one MDS case after benzole agent exposure additions are frequent, considered as imbalanced translocations translocations: translocations or dicentrics involving 12p are mostly associated with loss of 12p material; a lot of partner bands are described; chromosome 12 breakpoint is most often localized in 12p13, involving ETV6 gene, with fusion of 5' end of ETV6 with 3' end of the partner, and sometimes accompanied with a concomitant deletion of the other ETV6 allele: t(3;12)(q23;p12.3): described as reciprocal and recurrent, involving ETV6 (heterogeneous breakpoints described) and EVI1, and associated with a poor prognosis. t(4;12)q11q13;p12;p13): associated with specific clinical features: CD7-positive ANLL, three-lineage dysplasia, blood and bone marrow basophilia t(5;12)(q33;p13): recurrent, described in chronic myelomonocytic leukemia: fusion between HLH domain of ETV6 and transmembrane and cytoplasmic kinase domains of PDGFRb; a variant t(10;12)(q24;p13) is described in MDS in progression with eosinopilia and monocytosis. t/dic(12;13): representing up to 20% of 12p rearrangements in one study, associated with a poor prognosis t(12;22)(p13;q11): resulting in MN1-ETV6 fusion gene (where breakpoint, 5' of, or in, ETV6 HLH domain, is the sole exception), and reported in myeloid malignancies (ANLL and MDS) other translocations involving ETV6: t(5;12)(q31;p12) in "atypical CML", t(6;12)(p21;p13) in MDS, t(7;12)(p15;p13), t(7;12)(q36;p13) in ANLL, t(9;12;14)(q34;p13;q22) in ANLL, ... and the never-up-to-date following list: t(6;12)(q23;p13), t(12;17)(p11.2;q11), t/dic(12;20)(p12-p13;p11.2-q13), i(12p) where implication of ETV6 gene is not yet proven. |
| Probes | from telomere to centromere: corresponding to D12S1455: PAC9015; to CCND2: C139C5, C140H4, C146H1, C213C1 to PRB: CPRB to ETV6: yacs 958B8, 964C10, cosmids: C5OF4, C163E7, C179AB(5'), C148B6(3') to CDKN1B: 123C12, 142C5 to KRAS2: 153F12 |
| Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation. |
| Golub TR, Barker GF, Lovett M, Gilliland DG |
| Cell. 1994 ; 77 (2) : 307-316. |
| PMID 8168137 |
| |
| Translocation (12;22) (p13;q11) in myeloproliferative disorders results in fusion of the ETS-like TEL gene on 12p13 to the MN1 gene on 22q11. |
| Buijs A, Sherr S, van Baal S, van Bezouw S, van der Plas D, Geurts van Kessel A, Riegman P, Lekanne Deprez R, Zwarthoff E, Hagemeijer A |
| Oncogene. 1995 ; 10 (8) : 1511-1519. |
| PMID 7731705 |
| |
| TEL gene is involved in myelodysplastic syndromes with either the typical t(5;12)(q33;p13) translocation or its variant t(10;12)(q24;p13). |
| Wlodarska I, Mecucci C, Marynen P, Guo C, Franckx D, La Starza R, Aventin A, Bosly A, Martelli MF, Cassiman JJ |
| Blood. 1995 ; 85 (10) : 2848-2852. |
| PMID 7742547 |
| |
| Fluorescence in situ hybridization analysis of t(3; 12)(q26; p13): a recurring chromosomal abnormality involving the TEL gene (ETV6) in myelodysplastic syndromes. |
| Raynaud SD, Baens M, Grosgeorge J, Rodgers K, Reid CD, Dainton M, Dyer M, Fuzibet JG, Gratecos N, Taillan B, Ayraud N, Marynen P |
| Blood. 1996 ; 88 (2) : 682-689. |
| PMID 8695816 |
| |
| TEL and KIP1 define the smallest region of deletions on 12p13 in hematopoietic malignancies. |
| Sato Y, Suto Y, Pietenpol J, Golub TR, Gilliland DG, Davis EM, Le Beau MM, Roberts JM, Vogelstein B, Rowley JD |
| Blood. 1995 ; 86 (4) : 1525-1533. |
| PMID 7632960 |
| |
| Deletions of CDKN1B and ETV6 in acute myeloid leukemia and myelodysplastic syndromes without cytogenetic evidence of 12p abnormalities. |
| Andreasson P, Johansson B, Arheden K, Billstrˆm R, Mitelman F, Hˆglund M |
| Genes, chromosomes & cancer. 1997 ; 19 (2) : 77-83. |
| PMID 9171997 |
| |
| Fluorescence in situ hybridization analyses of hematologic malignancies reveal frequent cytogenetically unrecognized 12p rearrangements. |
| Andreasson P, Johansson B, Billstrˆm R, Garwicz S, Mitelman F, Hˆglund M |
| Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1998 ; 12 (3) : 390-400. |
| PMID 9529134 |
| |
| Correlation of cytogenetic, molecular cytogenetic, and clinical findings in 59 patients with ANLL or MDS and abnormalities of the short arm of chromosome 12. |
| Streubel B, Sauerland C, Heil G, Freund M, Bartels H, Lengfelder E, Wandt H, Ludwig WD, Nowotny H, Baldus M, Grothaus-Pinke B, Bˆºchner T, Fonatsch C |
| British journal of haematology. 1998 ; 100 (3) : 521-533. |
| PMID 9504635 |
| |
| Fluorescence in situ hybridization characterization of new translocations involving TEL (ETV6) in a wide spectrum of hematologic malignancies. |
| Wlodarska I, La Starza R, Baens M, Dierlamm J, Uyttebroeck A, Selleslag D, Francine A, Mecucci C, Hagemeijer A, Van den Berghe H, Marynen P |
| Blood. 1998 ; 91 (4) : 1399-1406. |
| PMID 9454771 |
| |
