MCL1 as putative target in pancreatoblastoma

Virchows Arch. 2022 Aug;481(2):265-272. doi: 10.1007/s00428-022-03349-w. Epub 2022 Jun 7.


Pancreatoblastoma (PB) is a rare tumor of the pancreas. In case of metastases, the treatment options are sparse and targeted approaches are not developed. We here evaluate MCL1 amplification as a putative target in PB.Thirteen samples from adult (10/13) and pediatric patients (3/13) were collected. Three of these samples had been previously subjected to whole-exome sequencing (2 cases) or whole-genome sequencing (1 case) within a precision oncology program (NCT/DKTK MASTER), and this analysis had shown copy number gains of MCL1 gene. We established a fluorescence in situ hybridization (FISH) test to assess the copy number alterations of MCL1 gene in 13 formalin-fixed paraffin-embedded PBs, including the 3 cases assessed by genome sequencing. FISH analysis showed the amplification of MCL1 in 2 cases (both were adult PB), one of which was a case with the highest copy number gain at genomic analysis. In both cases, the average gene copy number per cell was ≥ 5.7 and the MCL1/1p12 ratio was ≥ 2.4. Our data support MCL1 as a putative target in PB. Patients with MCL1-amplified PB might benefit from MCL1 inhibition. Sequencing data is useful to screen for amplification; however, the established FISH for MCL1 can help to determine the level and cellular heterogeneity of MCL1 amplification more accurately.

Keywords: Amplification; FISH; MCL1; NCT MASTER; Pancreatoblastoma; Whole-genome sequencing.

MeSH terms

  • Adult
  • Child
  • Gene Amplification
  • Humans
  • In Situ Hybridization, Fluorescence
  • Myeloid Cell Leukemia Sequence 1 Protein* / genetics
  • Pancreatic Neoplasms* / genetics
  • Pancreatic Neoplasms* / pathology


  • MCL1 protein, human
  • Myeloid Cell Leukemia Sequence 1 Protein

Supplementary concepts

  • Pancreatoblastoma