dic(7;9)(p11-13;p11)

2019-04-01   Mary J Underdown , Mary J Underdown , Mary J Underdown , Mary J Underdown 

1.Department of Pediatrics, Wake Forest School of Medicine, Winston Salem, North Carolina (MJU); Section of Pediatric Hematology-Oncology, Department of Pediatrics, Wake Forest School of Medicine, Winston Salem, North Carolina (DEK, TBR); Department of Pathology, Wake Forest School of Medicine, Winston Salem, USA (MJP), Medical Center Boulevard, Winston Salem, NC, USA 27157; dkram@wakehealth.edu
2.Childrens Cancer Research Institute, Kinderspitalgasse 6, A-1090 Vienna, Austria

Abstract

Dicentric (7;9)(p11-13;p11) is a rare but recurrent abnormality in pediatric and adult precursor B acute lymphoblastic leukemia (B-ALL). The rarity precludes a deep understanding of its biology and associated prognosis. However, recent findings have correlated dic(7;9) and PAX5 mutations, highlighting this cytogenetic events involvement in leukemogenesis and may also shed light on the overall prognosis of dic(7;9) B-ALL.

Clinics and Pathology

Disease

ALL

Phenotype stem cell origin

FAB L1 phenotype; pre-B immunophenotype, cIg+ or cIg-

Epidemiology

There have been 36 cases of dic(7;9)(p11-13;p11) currently identified in the literature, 17 (47.2%) of which are pediatric cases. This rare translocation makes up < 1% of childhood ALL, It is most commonly found in younger children, age ≤ 6 years; dic(7;9)(p11-13;p11) is found in approximately 3% of childhood ALL with 9p abnormalities and has been associated with B-ALL with t(9;22), or Philadelphia chromosome positive ALL.

Clinics

The most common clinical manifestations of dic(7;9) noted in the literature include age female, T- and B-ALL with B-cell predominance, leukocytosis

Prognosis

Favorable prognostic indicators in ALL include: age 1-10 years, female sex, Caucasian or Asian ethnicity, WBC count

Cytogenetics

Note

Several dicentric chromosomes found in childhood ALL are formed from the q arms of chromosomes 7, 9, 12, and, 17 with partial loss of the respective p arms.
Atlas Image
Figure 2: FISH image depicting 7; dic 7-9; 9 with centromeric probes of 7 and 9 fused - Courtesy Department of Pathology, Wake Forest School of Medicine, Winston Salem, USA.

Cytogenetics morphological

Unbalanced; In most cases, formation of a dicentric chromosome resulting in partial monosomies of 7p and 9p -> hypodiploid with 45 chromosomes. However, hyperdiploidy (56 chromosomes) has been identified.

Additional anomalies

del(6q), dup(1p), del(8p),...

Genes Involved and Proteins

Note
Genes involved are unknown. , A recent study by Bastian, et. al. found 19/250 pediatric and adult patients with B-cell precursor ALL harbored PAX5 mutations. Of these patients with PAX5 mutations, 12/19 (63%) had alterations in chromosome 9, though the specific cytogenetic alterations were not reported (Bastian and Schroeder, 2019).
 , A large cohort study out of St. Judes identified 17/1988 (0.86%) patients with dic(7;9) translocation; of those, 11/17 (65%) had a PAX5 alteration or mutation. While the PAX5 gene is located on 9p13.2, 5/11 (45%) cases with dic(7;9)(p11;p11) were associated with PAX5 alterations. This study found two distinct subtypes of B-ALL characterized by PAX5 alterations: the first (n=148) which harbor diverse PAX5 alterations (including rearrangements, sequence mutations, and focal intragenic amplifications) and the second (n=44) which harbor a particular nonsilent sequence mutation, PAX5 p.Pro80Arg. As a group of all PAX5, the 5-year event-free survival was variable, ranging from 50% to 75% (Gu and Churchman, 2019).
Gene name
PAX5
Location
9p13.2
Note
Recent studies have shown an association between dic(7;9) and PAX5 mutation. PAX5 encodes the B lymphoid transcription factor gene and is vitally important in regulating B cell lineage differentiation. PAX5 alterations may lead to arrested B-cell development in the pro-B-cell stage and may be central events in B lymphoid leukemogenesis (Shah and Schrader, 2013).

Bibliography

Pubmed IDLast YearTitleAuthors
84183691993Collaborative study of karyotypes in childhood acute lymphoblastic leukemias. Groupe Français de Cytogénétique Hématologique.
308426092019PAX5 biallelic genomic alterations define a novel subgroup of B-cell precursor acute lymphoblastic leukemia.Bastian L et al
22944361990Deletions of interferon genes in acute lymphoblastic leukemia.Diaz MO et al
306432492019PAX5-driven subtypes of B-progenitor acute lymphoblastic leukemia.Gu Z et al
149992942004Deletion of 7p or monosomy 7 in pediatric acute lymphoblastic leukemia is an adverse prognostic factor: a report from the Children's Cancer Group.Heerema NA et al
264659872015Acute Lymphoblastic Leukemia in Children.Hunger SP et al
282976282017Genetic Basis of Acute Lymphoblastic Leukemia.Iacobucci I et al
273419962016Chromosomal aberrations in childhood acute lymphoblastic leukemia: 15-year single center experience.Jarosova M et al
111068132000Screening for specific chromosome involvement in hematological malignancies using a set of seven chromosome painting probes. An alternative approach for chromosome analysis using standard FISH instrumentation.Nacheva EP et al
169385752006Dicentric (7;9)(p11;p11) is a rare but recurrent abnormality in acute lymphoblastic leukemia: a study of 7 cases.Pan J et al
146692942003Reassessment of the prognostic significance of hypodiploidy in pediatric patients with acute lymphoblastic leukemia.Raimondi SC et al
240136382013A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia.Shah S et al
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98066641998Clinical significance of Philadelphia chromosome positive pediatric acute lymphoblastic leukemia in the context of contemporary intensive therapies: a report from the Children's Cancer Group.Uckun FM et al
95950401998Detection of chromosome over- and underrepresentations in hyperdiploid acute lymphoblastic leukemia by comparative genomic hybridization.Wong N et al

Summary

Atlas Image
Figure 1: dic(7;9)(p11-13;p11) G-banding - Courtesy Cytogenetics Laboratory of the CCRI, Childrens Cancer Research Institute, Vienna.

Citation

Mary J Underdown ; Mary J Underdown ; Mary J Underdown ; Mary J Underdown

dic(7;9)(p11-13;p11)

Atlas Genet Cytogenet Oncol Haematol. 2019-04-01

Online version: http://atlasgeneticsoncology.org/haematological/1054/dic(7;9)(p11-13;p11)

Historical Card

2005-09-01 dic(7;9)(p11-13;p11) by  Sabine Strehl 

Childrens Cancer Research Institute, Kinderspitalgasse 6, A-1090 Vienna, Austria