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. 2015 Jun;22(3):L13-8.
doi: 10.1530/ERC-15-0108. Epub 2015 Apr 21.

Epigenetic dysregulation and poorer prognosis in DAXX-deficient pancreatic neuroendocrine tumours

Christodoulos P Pipinikas  1 , Harpreet Dibra  1 , Anna Karpathakis  1 , Andrew Feber  1 , Marco Novelli  1 , Dahmane Oukrif  1 , Guiseppe Fusai  1 , Roberto Valente  1 , Martyn Caplin  1 , Tim Meyer  2 , Andrew Teschendorff  2 , Christopher Bell  1 , Tiffany J Morris  1 , Paolo Salomoni  1 , Tu-Vinh Luong  1 , Brian Davidson  1 , Stephan Beck  1 , Christina Thirlwell  3
Affiliations

Epigenetic dysregulation and poorer prognosis in DAXX-deficient pancreatic neuroendocrine tumours

Christodoulos P Pipinikas et al. Endocr Relat Cancer. 2015 Jun.
No abstract available

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Figures

Figure 1
Figure 1
(A) Details of the study cohort. (B and C) Kaplan–Meier survival curves for ATRX- and DAXX-negative cases (n=17) as compared to ATRX/DAXX-positive cases (n=17) and ATRX-negative (n=8) and DAXX-negative (n=9) cases analysed independently and compared to ATRX/DAXX-positives cases respectively. The 5-year PFS was 85% for positive cases, 52% for ATRX-negative cases and 16% for DAXX-negative cases. (D) Unsupervised cluster analysis using the top 1000 MVPs that showed segregation of ATRX-negative (in green) and DAXX-negative (in orange) tumours as compared to normal pancreatic tissue. Of the six ATRX/DAXX-negative tumour samples (from six cases) that clustered with the normal control pancreatic samples, only one case (G1, DAXX-negative) progressed (PFS 51 months), and two cases had no follow-up data. Of the six metastatic samples included in this study, two of them (both DAXX-negative) had a matched G1 tumour sample. One of them grouped tightly with the G1 primary tumour. DNA methylation values (β-value 0–1) are represented using a colour scale, where yellow=low methylation and blue=high methylation. Samples are shown on the x-axis, and probes are shown on the y-axis. (E) Confirmation of tumour segregation primarily by grade and then by ATRX or DAXX status using the top 1000 MVPs. (F) Copy number variation (CNV) profiles associated with low and intermediate PNETs. The top panel demonstrates increasing CNV across the genome for low-grade (G1, ki-67 <2%) tumours, with the least CNV occurring in the ATRX/DAXX-positive primary (left). Increasing CNV alterations are seen in the ATRX/DAXX-negative tumour (middle) and most CNV alterations occur in the ATRX/DAXX-negative G1 liver metastasis (right). The same is observed in intermediate grade (G2, ki-67 3–20%) tumours in the bottom panel. Segmented copy numbers are shown as a red line, and sequential chromosomes are shown in green and black (chr. 1–22).
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References

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