del(7)(p11-15) solely

2017-06-01   Adriana Zamecnikova 

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

Abstract

Complete or partial loss of chromosome 7 is a recurrent cytogenetic abnormality that may be observed in both de novo and therapy-related hematopoietic disorders. It predominantly presents as monosomy 7 or deletion of the long arm of chromosome 7, often associated with an unfavorable prognosis. Deletions of the short arm of chromosome 7, originated from either a terminal or an interstitial deletion are less frequent and their pathological significance is less well characterized.

Clinics and Pathology

Disease

Myeloid malignancies and acute lymphoblastic leukemia (ALL).

Etiology

Deletion of 7p as the sole abnormality occurs in disorders with myelodysplastic or myeloproliferative features and acute lymphoblastic leukemia, and may therefore affect early hematopoietic progenitor cells.

Epidemiology

Myeloproliferative disorders mainly: chronic myeloproliferative disorder in 9 (balanced sex ratio; 4 males and 5 females aged 53 to 79 years old, median age 63 years) (Bernstein et al., 1980; CML Yunis et al., 1986; Obeid et al., 1989; Palka et al., 1990; Rodjer et al., 1990; Ohyashiki et al., 1993; Pedersen-Bjergaard et al., 1993; Lezon-Geyda et al., 2001; Maciejewski et al., 2002) and AML in 10 patients (4 males and 6 females, aged 0 to 80 years, median age 0 years) (Bernstein et al., 1984; Testa et al., 1985; Mecucci et al., 1989; Abruzzo et al., 1992; Veldman et al., 1997; Chessells et al., 2002; Babicka et al., 2007; Blink et al., 2012). Male prevalence and prevalence of T-cell phenotype and in ALL (6 males and 2 females aged 3 to 50 years, median age 25 years) (Kaneko et al., 1989; Berger et al., 1990; Bernard et al., 2001; Berger et al., 2003; Douet-Guilbert et al., 2004; Mullighan et al., 2009; Russell et al., 2009; Safavi et al., 2015). 5 patients with myeloid malignancies had secondary disorders treated for a previous malignancy (Mecucci et al., 1989; Rodjer et al., 1990; Abruzzo et al., 1992; Pedersen-Bjergaard et al., 1993). Three patients were Down syndrome patients (Table 1).
Chronic myeloproliferative disorders
1F/64CMD46,XX,del(7)(p11)
2M/71RAEB46,XY,del(7)(p11p22)
3F/62CMMoL46,XX,del(7)(p11)
4F/68RAEB46,XX,del(7)(p13)
5M/62RA45,XY,-10/46,XY,del(7)(p13p14)       multiple myeloma, chemotherapy
6FRA46,XX,del(7)(p14)
7F/63MDS46,XX,del(7)(p11) 46,XX,-7,+21       multiple myeloma, chemotherapy
8M/76MDS46,XY,del(7)(p12p15)
9M/53RA47,XY,del(7)(p13p22)
Acute myeloid leukemia
10M/7AML-M246,XY,del(7)(p11)
11M/51AML-M146,XY,del(7)(p1?5)
12F/20AML-M446,XX,del(7)(p14
13M/47AML-M246,XY,del(7)(p12p21)       Hodgkin disease, chemotherapy, radiotherapy
14F/80AML-M446,XX,del(7)(p12p21)       polycythemia vera, chemotherapy, radiotherapy
15F/11AML46,XX,del(7)(p12)       mature B-cell neoplasm, chemotherapy
16F/57AML-M747,XX,del(7)(p?),+21c
17F/0AML-M746,XX,del(7)(p15)
18M/55AML-M046,XY,del(7)(p12)/46,idem,t(2;2)(q31;q35)
19F/1AML47,XX,del(7)(p11),+21c
Acute lymphoblastic leukemia
20M/14T-ALL46,XY,del(7)(p15)
21M/25T-ALL46,XY,del(7)(p13p15)
22M/25T-ALL46,XY,del(7)(p13)
23M/29T-ALL46,XY,del(7)(p11p15)
24M/50T-ALL46,XY,del(7)(p12)
25FALL47,XX,del(7)(p13p15),+21c
26F/3B-ALL47-48,XX,+17,del(20),+21,inc/46,XX,del(7)(p11)
27M/30T-ALL46,XY,del(7)(p13)

Abbreviations: M, male; F, female; CMD, chronic myeloproliferative disorder; RAEB, refractory anemia with excess of blasts; MDS, myelodysplastic syndrome; CMMoL, chronic myelomonocytic leukemia; RA, refractory anemia; AML-M2, acute myeloblastic leukemia with maturation; AML-M1, acute myeloblastic leukemia without maturation; AML-M4, acute myelomonocytic leukemia; AML, acute myeloid leukemia; AML-M7, acute megakaryoblastic leukemia; AML-M5, acute monoblastic leukemia; AML-M0, acute myeloblastic leukemia with minimal differentiation, ALL, acute lymphoblastic leukemia/lymphoblastic lymphoma.
1. Bernstein et al., 1980; 2. Yunis et al., 1986; 3. Obeid et al., 1989; 4. Palka et al., 1990. 5. Rodjer et al., 1990; 6. Ohyashiki et al., 1993; 7. Pedersen-Bjergaard et al., 1993; 8. Lezon et al., 2001; 9. Maciejewski et al., 2002; 10. Bernstein et al., 1984; 11. Testa et al., 1985; 12-14. Mecucci et al., 1989; 15. Abruzzo et al., 1992; 16. Veldman et al., 1997; 17. Chessells et al., 2002; 18. Babicka et al., 2007; 19. Blink et al., 2012; 20. Kaneko et al., 1989; 21. Berger et al., 1990; 22. Bernard et al., 2001; 23. Berger et al., 2003; 24. Douet-Guilbert et al., 2004; 25. Mullighan et al., 2009; 26. Russell et al., 2009; 27. Safavi et al., 2015.

Cytogenetics

Represents as interstitial (9 cases) or terminal deletion (18 patients) with various breakpoints.

Prognosis

Deletion of 7p, appears to confer increased risk of treatment failure and inferior outcome, same as it observed with monosomy 7 in myeloid malignancies. Similarly, event-free survival and survival for patients with monosomy 7 or del(7p), but not of patients with del(7q), were significantly worse in ALL patients than those lacking these abnormalities suggesting the critical region of loss may be on the p-arm (Mecucci et al., 1989; Heerema et al. 2004).

Genes Involved and Proteins

Note
Germinal Mutations Deletions of the short arm of chromosome 7 that contains the GLI3 (GLI family zinc finger 3) gene at 7p14.1 are responsible for some cases of Greig cephalopolysyndactyly contiguous gene deletion syndrome, a disorder that affects development of the limbs, head, face that may be associated with intellectual disability. Chromosomal deletion or mutation within the TWIST1 (twist family bHLH transcription factor 1) gene at 7p21.1 is observed in Saethre-Chotzen syndrome associated with intellectual disability and developmental delay.

Result of the Chromosomal Anomaly

Oncogenesis

Chromosome 7p deletion is a recurrent cytogenetic abnormality that may be observed at initial presentation or may emerge during disease progression. Terminal or interstitial 7p deletions result in loss of the deleted material, supporting the existence of tumor-suppressor genes in that region. While no consistent region of loss was identified, these chromosomal deletions may contain areas harboring multiple functionally linked genes whose loss of function is thought to be the major event in disease initiation or progression. Most 7p losses involve large chromosomal regions, therefore it is likely that a cluster of cooperating tumor-suppressor genes collectively promote oncogenesis in dosage-dependent manner.

Bibliography

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Summary

Atlas Image
del(7)(p11-15)  Partial karyotypes showing deletions of the short arms of chromosome 7. Hybridization with Vysis D7S486 (7q31)/CEP 7 probe (Abbott moleculars, US) showing deletion of 7p proximal to chromosome 7 centromere. u2013 Courtesy Adriana Zamecnikova

Citation

Adriana Zamecnikova

del(7)(p11-15) solely

Atlas Genet Cytogenet Oncol Haematol. 2017-06-01

Online version: http://atlasgeneticsoncology.org/haematological/1796/del(7)(p11-15)

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