dic(5;17)(q11-14;p11-13)
2016-12-01 Soad Al Bahar , Adriana Zamecnikova Affiliation1.Kuwait Cancer Control Center, Department of Hematology [email protected]
Abstract
Complete or partial monosomies of the long arm of chromosome 5 and/or 17p are common findings in myeloid malignancies, particularly in therapy-related myeloid disorders. They usually result from interstitial or terminal deletions and less frequently from unbalanced rearrangements such as dicentric chromosomes. One of the recurring unbalanced translocation in myeloid malignancies is the unbalanced dicentric translocation dic(5;17)(q11-14;p11-13) that results in complete or partial monosomy for the long arm of chromosome 5 and the short arm of chromosome 17.
Clinics and Pathology
Disease
Chronic myeloproliferative neoplasms and acute myeloid leukemia (AML)
16 patients had a primary myelodysplastic syndrome (MDS) (Knapp et al., 1985; Herry et al., 2007; Lange et al., 2010) or de novo AML (Huret et al., 1991; Kwong et al., 1994; Arkesteijn et al., 1996; Tosi et al 1996; Wang et al., 1997; Mrozek et al., 2002; Zatkova et al., 2006; Herry et al., 2007; Hangai et al., 2013) and 2 patients had chronic myelogenous leukemia in advanced phase (Hagemeijer et al., 1981; Wang et al., 1997). 23 patients developed therapy-related MDS (Hatzis et al., 1995; Wang et al 1997; Andersen et al., 2005; Andersen et al., Andersen et al., 2008) or AML (Kerim et al., 1991; Heyn et al., 1994; Wang et al., 1997; Nakamori et al., 2003; Andersen et al., 2005; McNerney et al., 2014) after cytotoxic treatment and/or radiotherapy (Table 1).
Table 1. Reported patients with dic(5;17)(q11-14;p11-13).
Abbreviations: CML, chronic myeloid leukemia; RAEB, Refractory anemia with excess of blasts; AML-M2, Acute myeloblastic leukemia with maturation (FAB type M2); AML-M1, Acute myeloblastic leukemia without maturation (FAB type M1); AML, Acute myeloid leukemia, NOS; AML-M6, Acute erythroleukemia (FAB type M6); MDS, Myelodysplastic syndrome; AML-M7, Acute megakaryoblastic leukemia (FAB type M7).
1. Hagemeijer et al., 1981; 2. Knapp et al., 1985; 3. Huret et al., 1991; 4. Kerim et al., 1991; 5. Heyn et al., 1994; 6. Kwong et al., 1994; 7. Hatzis et al., 1995; 8. Arkesteijn et al., 1996; 9-10. Tosi et al., 1996; 11-24. Wang et al., 1997; 25.Mrozek et al., 2002; 26. Nakamori et al., 2003; 27.Andersen et al., 2005; 28-33.Andersen et al., 2005; 34. Zatkova et al., 2006; 35-37. Herry et al., 2007; 38. Andersen et al., 2008; 39.Lange et al., 2010; 40. Hangai et al., 2013; 41. McNerney et al., 2014.
16 patients had a primary myelodysplastic syndrome (MDS) (Knapp et al., 1985; Herry et al., 2007; Lange et al., 2010) or de novo AML (Huret et al., 1991; Kwong et al., 1994; Arkesteijn et al., 1996; Tosi et al 1996; Wang et al., 1997; Mrozek et al., 2002; Zatkova et al., 2006; Herry et al., 2007; Hangai et al., 2013) and 2 patients had chronic myelogenous leukemia in advanced phase (Hagemeijer et al., 1981; Wang et al., 1997). 23 patients developed therapy-related MDS (Hatzis et al., 1995; Wang et al 1997; Andersen et al., 2005; Andersen et al., Andersen et al., 2008) or AML (Kerim et al., 1991; Heyn et al., 1994; Wang et al., 1997; Nakamori et al., 2003; Andersen et al., 2005; McNerney et al., 2014) after cytotoxic treatment and/or radiotherapy (Table 1).
Table 1. Reported patients with dic(5;17)(q11-14;p11-13).
| Sex/Age | Diagnosis | Karyotype | |
| 1 | M/26 | CML | 44-45,XY,dic(5;17)(q11;p11),t(9;22),r(18) blast crisis |
| 2 | M/57 | RAEB | 45,XY,dic(5;17)(q11;p11),-7,+8/46,idem,add(18)(q23),+mar |
| 3 | M/69 | AML-M2 | 45,XY,r(3),dic(5;17)(q14;p13),del(7)(q11),add(9)(p2?),add(9)(q34),-12,-13,i(21)(q10),+mar/90,idemx2 |
| 4 | M/71 | AML-M1 | 47,XY,+8/44,XY,-5,-17,-18,+mar/44,XY,dic(5;17)(q11;p11),-18/46,XY,dic(5;17),-18,+mar idiopathic myelofibrosis, chemotherapy |
| 5 | M/1 | AML | 45,XY,hsr(2)(q22),dic(5;17)(q11;p11),der(7)del(7)(q11)hsr(7)(q11),der(12)t(12;19)(p11;q12),-19, +mar embryonal rhabdomyosarcoma, chemotherapy, radiotherapy |
| 6 | M/77 | AML-M1 | 47,XY,+14/45,XY,dic(5;17)(q11;p11),dmin/95-96,XXY,-Y,-5,+9,+11,+12,+13,+13, +14,+14,+ 17 |
| 7 | F/59 | RAEB | 45,XX,dic(5;17)(q11;p11) acute promyelocytic leukemia, relapse, chemotherapy |
| 8 | M/45 | AML-M1 | 46,XY,t(1;15)(p21;q23),t(3;5)(q23;q12),ins(4;12)(q28;p?),dic(5;17)(q11;p11),der(7)t(7;18)(q11;q12)t(14;18)(q12;q23),+8,-14,del(18)(q12q23),add(19)(q23), +21 |
| 9 | F/63 | AML | 46,XX,dic(5;17)(q11;p11),-7,der(10)t(10;19)(p11;q11),-19,+2mar |
| 10 | M/75 | AML | 46,XY,-3,dic(5;17)(q11;p11),del(7)(q22q?),+8,+11,-15,+mar |
| 11 | M/66 | AML-M6 | 43,XY,der(5)t(5;12)(q13;q14),dic(5;17)(q13;p11),-7,dup(9)(q21q12),-12,-15, add(16)(q13),add(17)(p11),-18, +add(21)(p11),+mar/44,idem,+13 |
| 12 | F/64 | MDS | 45,XX,-7/45,XX,dic(5;17)(q11;p11)/44,XX,dic(5;17),der(7)t(7;13)(q11;q14), add(13)(q14),-17/44,XX,-3, dic(5;17),der(7)t(3;7)(p14;q32)/44,XX,-3,der(5)t (5;7)(q11;p1?5),dic(5;17),der(7)t(7;16)(p1?5;p13)t(3;7), der(16;17)t(16;17)(p13;p11)ins(16;5)(p13;q11q11),add(21)(q22) adenocarcinoma, chemotherapy, radiotherapy |
| 13 | F/50 | AML | 45,XX,dic(5;17)(q13;p11),inv(5)(p13q11)/46,idem,+8/44,idem,-11,add(16)(p13),der(19)t(11;19)(q11q25;p13) add(11)(q11) multiple myeloma, chemotherapy |
| 14 | F/64 | AML | 45,XX,add(1)(q42),add(4)(q2?5),dic(5;17)(q11;p11),der(6)t(6;12)(q21;q21),-12,+mar/46,idem,+8/46,idem,+11, der(11;11)t(11;11)(p15;q25)ins(11;?)(p15;?)/46,idem,+11,der(11;11),+13,-mar,+mar adenocarcinoma, chemotherapy |
| 15 | F/73 | AML | 43,XX,dic(3;22)(p21;p11),dic(5;17)(q11;p11),-7,+8,add(12)(p13),add(14)(p11), -16/44,idem,+mar adenocarcinoma, radiotherapy |
| 16 | F/48 | MDS | 46,XX,t(8;17)(p11;q22) or t(8;17)(p21;q23)/46,XX,del(7)(q22q34)/46,XX,t(2;18)(p21;p11)/ 46,XX,t(2;12)(q11;q21-22),t(11;17)(q13;q25)/45,XX,del(1) (p34p36),dic(5;17)(q13;p11),+8,-18 follicular lymphoma, chemotherapy, radiotherapy |
| 17 | M/55 | MDS | 44,XY,dic(5;17)(q13;p11),dic(19;20)(p13;q11)/45,idem,+mar Hodgkin disease, chemotherapy |
| 18 | F/81 | MDS | 47,XX,del(3)(p21p24),dic(5;17)(q13;p11),+8,+22/48,idem,+X adenocarcinoma, radiotherapy |
| 19 | M/58 | MDS | 45,XY,dic(5;17)(q11;p11),r(7)(p2?2q1?1)/45,idem,dic(5;17),i(9)(p10),del(13)(q12q14)/43,XY,dic(5;17),-7, dic(9;18)(q13;p11)/44,XY,dic(5;17),-7/46,XY,del(11)(q14q23) chronic lymphocytic leukemia, chemotherapy |
| 20 | M/73 | AML | 43,XY,-3,dic(5;17)(q11;p11),-7,+12,t(12;?12)(p13;q13-14),-18,+19,-22/42, idem,-12,del(22)(q11)/43,idem,-12,del(22),+del(22)/44,idem,-12,del(22),+del(22),+mar/42,idem,t(9;15)(p2?2;q2?1),-12,del(22) |
| 21 | M/57 | AML-M7 | 47,XY,dic(5;17)(q11;p11),-7,-13,add(19)(p13),+4mar |
| 22 | M/59 | CML | 45,XY,dic(5;17)(q11;p11),del(9)(q34) or del(9)(q34q34),t(9;22)(q34;q11)/45,idem,+22/45,XY,t(9;22),der(18) t(17;18)(q11;p11) |
| 23 | M/25 | AML | 44,XY,del(3)(p13),dic(5;17)(q11;p11),-7 Hodgkin disease, chemotherapy, radiotherapy |
| 24 | M/8 | AML | 45,XY,dic(5;17)(q11;p11),del(7)(q22q35)/46,idem,+21/44,idem,der(11;21)t(11;21)(p15;p13) ins(11;?)(p15;?) add(11)(q22) rhabdomyosarcoma, chemotherapy, radiotherapy |
| 25 | M/48 | AML-M2 | 45-46,XY,der(5)t(5;17)(q11;q11),r(11;11)(p15q25;q?),-17,+mar/47,idem,+der(5)t(5;17)(q11;q11)/44,XY,der(4) t(4;11)(q3?5;q13)ins(4;11)(q3?5;?)t(11;11)(q25;?),der(5)t(5;17),-11,-17/42,XY,dic(5;17)(q11;p11-12),-7,der(11)del(11)(q13q23)dup(11)(q24q22)t(11;12)(q2?2;q22),-12,der(16)del(16)(q22q24)?dup(16)(q24q24)t(7;16(q11;q24),-18 ? |
| 26 | M/54 | AML-M6 | 44,XY,dic(5;17)(q13;p11),-7,add(15)(q24)/44,idem,-dic(5;17),+mar 43,XY,dic(5;17),-7,add(12)(p11),add(15)(q24),-16 56,XY,+Y,+1,+2,add(3)(p13),add(4)(p11),+6,+14,+15,add(15)x2,add(19)(p13), +20,+4mar/113-116,idemx2,+8,+8,+5mar adenocarcinoma, chemotherapy |
| 27 | M/62 | AML-M1 | 43-47,X,-Y,dic(5;17)(q11;p11),der(5;17)t(5;17)t(13;17)(q?14;q?),-7,der(9)t(9;12)(q34;q?13),+der(10)del(10)(p?)del(10)(q?),-12,der(13;21)(q10;q10),i(13)(q10), der(18)t(14;18)(q?;p?)t(14;21)(q?24;q?11),der(18)t(9;18)(?;p11)t(9;14)t(9;21) Wegeners granulomatosis, chemotherapy |
| 28 | M/69 | MDS | 46,X,t(Y;16)(q12;q?),del(3)(p24p?),del(5)(q31q31),dic(5;17)(q11;p11),dup(19)(q?),+del(21)(q21)/48,idem,+18, +19,-dup(19),+22 Hodgkin disease, chemotherapy, radiotherapy |
| 29 | F/53 | MDS | 43,XX,dic(5;17)(q11;p11),dic(6;19)(p2?4;?),-21/43,XX,dic(5;17),-7,ider(21)(q10)del(21)(q22),-22,der(22)t(9;22)(q?;p11) adenocarcinoma, chemotherapy |
| 30 | F/86 | AML | 44,XX,dic(5;17)(q11;p11),-7,der(10)t(10;11)(q25;q22)/43,idem,del(3)(p21),dic(4;7)(q11;q11),+7,der(8)t(4;8) (q21;p21),-12,der(12)t(12;21)(p13;q22),der(21)t(12;21)(q?;q21)/43,idem,del(3),dic(4;7),+7,der(8)t(4;8),dup(11)(q23q23),-12,der(12)t(12;21),der(21)t(12;21) adenocarcinoma, chemotherapy |
| 31 | M/73 | AML | 44,XY,dic(5;17)(q11;p11),der(6)del(6)(p?)del(6)(q?),dup(6)(q?),-7,dup(8)(p?),ins(9;5)(q34;q31q31) Hodgkin disease, chemotherapy, radiotherapy |
| 32 | M/39 | AML-M1 | 45,XY,dic(5;17)(q11;p11),+11,-19,der(20)t(19;20)t(19;20)/43,idem,-11,-16/43-46,idem,dic(3;15)(p11;p11),-4, der(19)t(4;19)(?;q?),der(20)t(19;20)t(4;19) Hodgkin disease, chemotherapy, radiotherapy |
| 33 | M/76 | MDS | 45,XY,dic(5;17)(q11;p11),+6,der(6)t(6;11)(p23;q14-21)x2,del(7)(q22),dic(15;16)(p11;q11)/45,idem,+del(7)(q31),-del(7)(q22),+dup(7)(q31q31)/45,idem, +15,-dic(15;16),+del(16)(q12),-18 Hodgkin disease, chemotherapy |
| 34 | M/72 | AML-M1 | 47-49,XY,der(2;7)dic(2;7)(p23;q11)t(2;12)(q33;q11),dic(5;17)(q11;p12),+8,+r(11)x3,der(12)t(2;12)(p23;q11),+13 |
| 35 | F/32 | MDS | 45,XX,dic(5;17)(q11;p11),-7,+r/45,idem,add(14)(p11) |
| 36 | F/79 | MDS | 46,XX,dic(5;7)(q11;p11),idic(5)(q11),r(5),?dic(7;8)(q31;p22),?dic(12;17)(p12;q22) |
| 37 | M/69 | AML-M2 | 46,XY,dic(5;17)(q11;p11),-7,+add(11)(q25),+13,del(13)(q31)x2,-16,-17,-18, +3mar |
| 38 | M/69 | MDS | 46,X,t(Y;16)(q12;q?),del(3)(p24p?),del(5)(q13q31),dic(5;17)(q11;p11),dup(19)(q?),+del(21)(q21)/48,idem,+18,+19,-dup(19),+22 Hodgkin disease, chemotherapy, radiotherapy |
| 39 | M/73 | RAEB | 44-45,XY,dic(5;17)(q11;p11),+8,-13,-21,+1-2mar/45-47,idem,+13,t(15;18)(q10;q10),+i(21)(q10) |
| 40 | M/79 | AML-M6 | 44,XY,add(2)(q21),dic(5;17)(q13;p11),-7,+8,add(12)(p11),-15,-16,+mar |
| 41 | M/39 | AML | 45,XY,-3,r(5)(p14q11),-7,+der(19)t(3;19)(q2?5;q13)/44,XY,-3,dic(5;17)(q12;p11),-7,+mar/ 44,XY,t(3;15) (p2?3;q15),dic(5;12)(q12;p11),-7,add(10)(p13) squamous cell carcinoma, chemotherapy, radiotherapy |
Abbreviations: CML, chronic myeloid leukemia; RAEB, Refractory anemia with excess of blasts; AML-M2, Acute myeloblastic leukemia with maturation (FAB type M2); AML-M1, Acute myeloblastic leukemia without maturation (FAB type M1); AML, Acute myeloid leukemia, NOS; AML-M6, Acute erythroleukemia (FAB type M6); MDS, Myelodysplastic syndrome; AML-M7, Acute megakaryoblastic leukemia (FAB type M7).
1. Hagemeijer et al., 1981; 2. Knapp et al., 1985; 3. Huret et al., 1991; 4. Kerim et al., 1991; 5. Heyn et al., 1994; 6. Kwong et al., 1994; 7. Hatzis et al., 1995; 8. Arkesteijn et al., 1996; 9-10. Tosi et al., 1996; 11-24. Wang et al., 1997; 25.Mrozek et al., 2002; 26. Nakamori et al., 2003; 27.Andersen et al., 2005; 28-33.Andersen et al., 2005; 34. Zatkova et al., 2006; 35-37. Herry et al., 2007; 38. Andersen et al., 2008; 39.Lange et al., 2010; 40. Hangai et al., 2013; 41. McNerney et al., 2014.
Phenotype stem cell origin
Phenotype / cell stem origin de novo and therapy related myeloid malignancies.
Epidemiology
29 male and 12 female patients (sex ratio 2.4) aged 1 to 86 years (median age 63 years). There were 2 pediatric cases (aged 1 and 8 years), both of them developed AML after therapy for rhabdomyosarcoma.
Prognosis
Patients with 5q and/or 17p deletions and complex karyotypes represent an unfavorable cytogenetic prognostic category, particularly when the disorder is related to previous cytotoxic therapy.
Cytogenetics
Cytogenetics morphological
Presents as 1 normal chromosome 5 and 17 and a dic(5;17) chromosome that contains the short arm of chromosome 5, the long arm of chromosome 17 and centromeres of both chromosomes; breakpoints at or near the centromeres may be difficult to ascertain, the most common described breakpoints were q11 on chromosome 5 and p11 on 17p, reported in 31 out of 41 patients. Combining karyotyping with fluorescence in situ hybridization of centromere-specific probes for chromosomes 5 and 17 allows precise breakpoint definition and confirm the presence of both centromeres.
Additional anomalies
Sole anomaly in 1 MDS patient previously treated for acute promyelocytic leukemia and found in association with increased karyotype complexity in most of the cases. The most commonly observed anomaly was monosomy 7, observed in 19, while 7q deletion was found in 5 patients. Monosomy 5/5q- was found in 4 and +8 in 10 patients.
Genes Involved and Proteins
Result of the Chromosomal Anomaly
Oncogenesis
Deletion of 5q and 17p through formation of an unbalanced dicentric rearrangement is a non-random event in myeloid malignancies, particularly in therapy-related disorders. dic(5;17)(q11-14;p11-13) result in partial monosomy for 5q and 17p leading to altered gene dosages, affecting tumor suppressor genes. The key mechanism might be the combined loss of tumor suppressor genes in 5q and 17p containing the TP53 gene. It is likely that TP53 loss that is frequently accompanied by inactivating mutations in the remaining TP53 allele (Wang et al., 1997) represent one of the instigators of the genome instability that is manifested by complex karyotypes. Highly complex rearrangements containing unbalanced translocations, ring chromosomes, insertions, marker chromosomes, homogeneously staining regions, dicentric chromosomes and cytogenetically unrelated clones were overrepresented in patients with therapy-related myeloid malignancies, indicative of the role of mutagenic effect of previous therapy. The probable sequence of genetic events is unclear; however dic(5;17) usually presents with additional common anomalies such as monosomy 7/7q or 5/5q and trisomy 8, therefore the formation of dic(5;17) likely represent a therapy-induced abnormality that occurred during the multistep process of leukemogenesis
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 15645489 | 2005 | Centromeric breakage and highly rearranged chromosome derivatives associated with mutations of TP53 are common in therapy-related MDS and AML after therapy with alkylating agents: an M-FISH study. | Andersen MK et al |
| 8630983 | 1996 | The use of FISH with chromosome-specific repetitive DNA probes for the follow-up of leukemia patients. Correlations and discrepancies with bone marrow cytology. | Arkesteijn GJ et al |
| 6945934 | 1981 | Translocation (5p; 17q) in blast crisis of chronic myeloid leukemia. | Hagemeijer A et al |
| 23070126 | 2013 | Erythroleukemia showing early erythroid and cytogenetic responses to azacitidine therapy. | Hangai S et al |
| 7832190 | 1995 | Acute promyelocytic leukaemia (M3): relapse with acute myeloblastic leukaemia (M2) and dic(5;17) (q11;p11). | Hatzis T et al |
| 17556068 | 2007 | Evaluation of chromosome 5 aberrations in complex karyotypes of patients with myeloid disorders reveals their contribution to dicentric and tricentric chromosomes, resulting in the loss of critical 5q regions. | Herry A et al |
| 8202048 | 1994 | Acute myeloid leukemia in patients treated for rhabdomyosarcoma with cyclophosphamide and low-dose etoposide on Intergroup Rhabdomyosarcoma Study III: an interim report. | Heyn R et al |
| 1950371 | 1991 | Two additional cases of isochromosome 21q or translocation 21q21q in hematological malignancies. | Huret JL et al |
| 2009512 | 1991 | Trisomy 8 and an unbalanced t(5;17)(q11;p11) characterize two karyotypically independent clones in a case of idiopathic myelofibrosis evolving to acute nonlymphoid leukemia. | Kerim S et al |
| 3860707 | 1985 | Cytogenetic studies in 174 consecutive patients with preleukemic or myelodysplastic syndromes. | Knapp RH et al |
| 8143281 | 1994 | Cytogenetic triclonality in acute myeloid leukemia: a morphologic, immunologic and in situ hybridization study. | Kwong YL et al |
| 19998444 | 2010 | Telomere shortening and chromosomal instability in myelodysplastic syndromes. | Lange K et al |
| 24931631 | 2014 | The spectrum of somatic mutations in high-risk acute myeloid leukaemia with -7/del(7q). | McNerney ME et al |
| 11979548 | 2002 | Spectral karyotyping in patients with acute myeloid leukemia and a complex karyotype shows hidden aberrations, including recurrent overrepresentation of 21q, 11q, and 22q. | Mrózek K et al |
| 12601545 | 2003 | Therapy-related erythroleukemia caused by the administration of UFT and mitomycin C in a patient with colon cancer. | Nakamori Y et al |
| 8618441 | 1996 | Classification of deletions and identification of cryptic translocations involving 7q by fluorescence in situ hybridization (FISH). | Tosi S et al |
| 9365836 | 1997 | dic(5;17): a recurring abnormality in malignant myeloid disorders associated with mutations of TP53. | Wang P et al |
| 16736498 | 2006 | GAB2 is a novel target of 11q amplification in AML/MDS. | Zatkova A et al |
Summary
Note
Included are 5q11-14 and 17p11-13 breakpoints (breakpoints described at or near the centromeres), the related unbalanced der(5)t(5;17) and der(17)t(5;17) are not included.
Figure 1 dic(5;17)(q11.2~13;p11.2~13) G- banding: - Courtesy Ronnie Ghuman and Charles D. Bangs.
Citation
Soad Al Bahar ; Adriana Zamecnikova
dic(5;17)(q11-14;p11-13)
Atlas Genet Cytogenet Oncol Haematol. 2016-12-01
Online version: http://atlasgeneticsoncology.org/haematological/1164/dic(5
