Myeloid disorders, less frequently multiple myeloma and lymphoid malignancies

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

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.

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

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.