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Case Reports
. 2022 Mar 20;23(6):3347.
doi: 10.3390/ijms23063347.

Characterization of Chromosomal Breakpoints in 12 Cases with 8p Rearrangements Defines a Continuum of Fragility of the Region

Serena Redaelli  1 , Donatella Conconi  1 , Elena Sala  2 , Nicoletta Villa  2 , Francesca Crosti  2 , Gaia Roversi  1   2 , Ilaria Catusi  3 , Chiara Valtorta  3 , Maria Paola Recalcati  3 , Leda Dalprà  1   2 , Marialuisa Lavitrano  1 , Angela Bentivegna  1
Affiliations
Case Reports

Characterization of Chromosomal Breakpoints in 12 Cases with 8p Rearrangements Defines a Continuum of Fragility of the Region

Serena Redaelli et al. Int J Mol Sci. .

Abstract

Improvements in microarray-based comparative genomic hybridization technology have allowed for high-resolution detection of genome wide copy number alterations, leading to a better definition of rearrangements and supporting the study of pathogenesis mechanisms. In this study, we focused our attention on chromosome 8p. We report 12 cases of 8p rearrangements, analyzed by molecular karyotype, evidencing a continuum of fragility that involves the entire short arm. The breakpoints seem more concentrated in three intervals: one at the telomeric end, the others at 8p23.1, close to the beta-defensin gene cluster and olfactory receptor low-copy repeats. Hypothetical mechanisms for all cases are described. Our data extend the cohort of published patients with 8p aberrations and highlight the need to pay special attention to these sequences due to the risk of formation of new chromosomal aberrations with pathological effects.

Keywords: array CGH; chromosome instability; cytogenetics; molecular karyotype.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Graphical representation of chromosome 8 aberrations described in this study. Left: in the third column, from top to bottom, the identified breakpoints are reported from most distal to most proximal; in the middle, the alterations are specified as in the figure (see below); and in the first column, the cases in which they have been identified. Right: red bars: deletions (del); blue bars: duplications (dup). Green brackets show the most frequent breakpoint intervals: interval 1 is the most telomeric, in 8p23.3, from nt 184,617 to nt 221,611; intervals 2 and 3 are in 8p23.1, from nt 6,942,337 to nt 9,730,115 and from nt 10,029,424 to nt 12,627,630, respectively. The region of the 8q arm not shown in the figure is indicated by the N.
Figure 2
Figure 2
Upper panel: array CGH results of cases 1-3. Lower panel: Cytogenetics and FISH results of case 3. (A) QFQ-banded chromosome 8. (B) Partial metaphase after tricolor FISH with probes RP11-589N15 (blue signals), RP11-45016 (red signals), and RP11-139G9 (green signals). (C) Partial metaphase after dual-color FISH with probes RP11-589N15 (blue signals) and RP11-139G9 (green signals). (D) Partial metaphase after dual color FISH with probes RP11-45016 (red signals) and RP11-139G9 (green signals). (E) Array CGH ideogram showing the del inv dup(8p) region and the reciprocal mapping of FISH probes.
Figure 3
Figure 3
Cases 4, 5, and 6. QFQ-banded chromosomes for case 4 (left) and 5 (middle). Array CGH ideograms for case 4, 5, and 6 (from left to right). Asterisks (*) show benign CNVs.
Figure 4
Figure 4
Case 7. (A) QFQ-banded chromosome 8 (the white arrow indicates the anomalous chromosome). (B) GTG-banded chromosome 8. (C) Partial metaphase after FISH with specific subtelomeric probes of chromosome 8 (green: telomere 8p, red: telomere 8q). The anomalous chromosome 8 shows the 8q telomere on both extremities (white arrow). (D) Array CGH results. The red arrow indicates a very small duplication of the 8q telomere.
Figure 5
Figure 5
Cases 8, 9, and 10. (A) QFQ-banded chromosome 8 for cases 8 (left) and 9 (right), with the corresponding array CGH ideograms below. (B) QFQ-banded chromosome 8 of case 10 obtained from spontaneous metaphases of cytotrophoblasts. Array CGH results on chorionic villi (CV, left) and amniotic fluid (AF, right). No conventional cytogenetics were performed on amniotic fluid.
Figure 6
Figure 6
Cases 11 and 12. Array CGH results showing case 11 with a duplication (left) and case 12 with an 8p duplication and a 10q deletion due to an unbalanced maternal translocation t(8;10)(p22;q26.2) (right).
Figure 7
Figure 7
Schematic diagram of benign CNVs on 8p identified in our cohort. Defensin gene clusters and OR/FAM clusters are represented by colored arrows: red, α-defensin; green, β-defensin; pink, OR/FAM clusters. The direction of the arrows indicates cluster orientation. Purple vertical lines: OR7 family at 8p23.1. Horizontal lines: benign CNVs: losses are red; gains are blue. Line thickness: frequency of the CNV in our cohort where the thinnest is for ≤40 patients; the largest is for the most frequent CNV (≥500 patients); the middle lines are for intermediate situations (around 100 patients). The region of the 8q arm not shown in the figure is indicated by the N.
See this image and copyright information in PMC

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