der(12)t(1;12)(q11-21;p11-13)

2015-09-01   Adriana Zamecnikova , Soad Al Bahar 

1.Kuwait Cancer Control Center, Department of Hematology, Kuwait annaadria@yahoo.com

Abstract

Review on t(1;12)(q11-21;p11-13), with data on clinics.

Clinics and Pathology

Disease

Myeloid disorders, less frequently multiple myeloma and lymphoid malignancies

Note

The balanced t(1;12)(q21;p13) translocation results in a ETV6 / ARNT fusion gene.

Phenotype stem cell origin

16 cases with an unbalanced sex ratio (11 males/5 females aged 0 to 79-years old). Most cases were diagnosed with myeloid malignancies (10 patients; 7 males and 3 females aged 0 to 72 years old): 3 patients with refractory anemia (RA) (Pedersen-Bjergaard et al., 1998; Andersen et al., 2005; Gerr et al., 2006), among them 2 were treated for multiple myeloma (MM) (Pedersen-Bjergaard et al., 1998; Andersen et al., 2005) and 7 patients were diagnosed with acute myeloid leukemia (AML) (Trent et al., 1983; La Starza et al., 1999; Odero et al., 2001; Andersen et al., 2005; Fitzgibbon et al., 2005; Raghavan et al., 2005; Gerr et al., 2006; Tuborgh et al., 2013; Parihar et al., 2014). The AML cases were most often M5 AML (5/7) and in this small AML M5 series, 3 cases are found in infant patients. 3 cases were diagnosed with multiple myeloma (Calasanz et al., 1997; González et al., 2004; Gabrea et al., 2008) and 3 with lymphoid malignancies: chronic lymphocytic leukemia (CLL) (Miyamoto et al., 1981), Burkitts lymphoma (Schoch et al., 1995) and mature B-cell neoplasm (Kuroda et al., 2000) (Table 1).

Sex/Age

Disease

Karyotype

Ref.

Myeloid neoplasms

M/72

AML

46,XY,der(12)t(1;12)(q21;p13)

1

F/59

RA post MM

43,X,-X,t(3;21)(q26;q22),del(4)(p14p16),-6,-8,del(10)(p11),der(12)t(1;12)(q21;p12),-13,-14,-14,del(20)(p12),add(22)(q12),+3mar

2

M/55

AML-M6

48,XY,+8,der(12)t(1;12)(q21;p13),+mar/48,idem,add(7)(q?)

3

F/1

AML-M5

46,XX,t(9;11)(p22;q23),del(17)(p13),der(22)t(17;22)(p13;q13)/47,XX,+der(9)t(9;11),t(9;11),der(12)t(1;12)(q21;p12)

4

M/66

RAEBI-post MM

45-47,XY,+del(1)(p21),dic(1;7)(p11;q11),der(6)t(3;6)(?;p?22),t(6;21)(p?22;q22), dic(7;13)(p11;p11), der(12)t(1;12)(q21;p13)

5

M

AML-M5

46,XY,der(12)t(1;12)(q11;p11)

6

M

AML-M5

46,XY,der(12)t(1;12)(q11;p11)

7

M/63

RAEBI

47,XY,+8,add(9)(p11),+add(9)(q11),del(20)(p11),+21,add(21)(p11)x2/47, idem, der(1)del(1)(p34)t(1;21)(q12;p12),der(12)t(1;12)(q12;p12),add(14)(p11),-add(21)

8

M/0

AML-M5

47,XY,t(6;19;11)(p22;p13;q23),+der(6)t(6;11)(p22;q23)/48,idem,+8/48,idem,+8, der(12)t(1;12)(q11;p13)/48,X,der(Y)t(Y;1)(q12;q11),t(6;19;11),+der(6)t(6;11),+8

9

F/1

AML-M5

46,XX,der(12)t(1;12)(q12;p13)/46,XX,der(13)t(1;13)(q12;p12)

10

Multiple myeloma

M

MM

46,XY,del(5)(q13q22),der(10)t(1;10)(q11;p11),t(11;14)(q13;q32),der(14)t(11;14)/46,XY,del(5),t(11;14),der(12)t(1;12)(q11;p11),der(14)t(11;14)

11

M

MM

45,XY,der(12)t(1;12)(q21;p13),-13

12

F

MM

46-47,X,-X,der(1;16)(q10;p10),-4,+5,+7,t(8;22)(q24;q11),der(12)t(1;12)(q11-12;p13),-13,+del(15)(q12q13),der(17)(1;17)(q11-12;p13),+18,der(20)t(19;20) (?;q2?2),+21

13

B-cell neoplasms

M46

CLL

??,XY,del(1)(q?),t(1;10)(q11;p1?5),der(12)t(1;12)(q11;p12)

14

M/40

BL

46,XY,t(8;14)(q24;q32),der(12)t(1;12)(q21;p13),add(14)(q32)/46,idem,add(17)(p?),add(18)(p11)

15

F/79

B-cell neoplasm

48,XX,t(8;22)(q24;q11),der(12)t(1;12)(q21;p13),+17,+mar

16


TABLE 1
Abbreviations: Ref, reference; M, male; F, female; AML, acute myeloid leukemia; RA, refractory anemia; MM, multiple myeloma; RAEB, refractory anemia with excess of blasts; CLL, chronic lymphocytic leukemia; BL, Burkitts lymphoma.
References: 1. Trent et al., 1983; 2. Pedersen-Bjergaard et al., 1998; 3. La Starza et al., 1999; 4. Odero et al., 2001; 5. Andersen et al., 2005; 6. Fitzgibbon et al., 2005; 7. Raghavan et al., 2005; 8. Gerr et al., 2006; 9. Tuborgh et al., 2013; 10. Parihar et al., 2014; 11. Calasanz et al., 1997; 12. González et al., 2004; 13. Gabrea et al., 2008; 14. Miyamoto et al., 1981; 15. Schoch et al., 1995; 16. Kuroda et al., 2000.

Prognosis

Unknown; may be unfavorable in association with complex karyotypes and in association with poor-risk genetic features.

Genes Involved and Proteins

Note
This unbalanced translocation is likely to be molecularly heterogeneous and whether the same gene(s) are involved in both myeloid and lymphoid malignancies is unknown.

Result of the Chromosomal Anomaly

Oncogenesis

Unbalanced translocations between the long arm of chromosome 1 and the short arm of chromosome 12 are infrequent but might be relatively specific to myeloid-lineage malignancies. Although cytogenetically heterogeneous, der(12)t(1;12)(q11-21;p11-13) results in a gain of 1q leading to genomic imbalances. Gains/amplification of 1q are common in a broad spectrum of myeloid and lymphoid haematological malignancies indicating that that genes of the 1q region may provide selective growth advantages for the leukemic cells in a variety of neoplasms.
The unbalanced der(12)t(1;12)(q11-21;p11-13) may be present as the sole anomaly or in association with complex karyotypes, implicating that it may have a key role in disease initiation and/or progression. Alternatively, it is possible that genes on the 12p11-p13 region may also be involved in disease pathogenesis either as a result of the chromosome translocation and/or deletions. Notably, chromosome 12 breakpoint in der(12)t(1;12)(q11-21;p11-13) is most often localized on 12p13, that include the TEL/ETV6 gene, therefore it is possible that ETV6 may be affected by the translocation, at least in some patients. In addition, 12p rearrangements are frequently accompanied by small interstitial deletions that include ETV6 and CDKN1B among other genes. Thus, haploinsufficiency or loss of tumor suppressor function of genes located on the 12p11-p13 region may play a role in oncogenesis. Whether genes located on the 12p11-p13 region are involved in this aberration has not been determined.

Bibliography

Pubmed IDLast YearTitleAuthors
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183816412008Secondary genomic rearrangements involving immunoglobulin or MYC loci show similar prevalences in hyperdiploid and nonhyperdiploid myeloma tumors.Gabrea A et al
173749642006Fluorescence in situ hybridization reveals closely correlated results in cytological and histological specimens of hematological neoplasias compared to conventional cytogenetics.Gerr H et al
154772062004The value of fluorescence in situ hybridization for the detection of 11q in multiple myeloma.González MB et al
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64566451981Abnormalities of chromosome no. 1 related to blood dyscrasias: study of 10 cases.Miyamoto K et al
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240192272014Jumping translocation in a case of de novo infant acute myeloid leukemia.Parihar M et al
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237355622013Complex three-way translocation involving MLL, ELL, RREB1, and CMAHP genes in an infant with acute myeloid leukemia and t(6;19;11)(p22.2;p13.1;q23.3).Tuborgh A et al

Summary

Atlas Image

Citation

Adriana Zamecnikova ; Soad Al Bahar

der(12)t(1;12)(q11-21;p11-13)

Atlas Genet Cytogenet Oncol Haematol. 2015-09-01

Online version: http://atlasgeneticsoncology.org/haematological/1652/der(12)t(1;12)(q11-21;p11-13)

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