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Purpose <p>Crooke cell adenomas (CCAs) are rare histological subtype of corticotroph pituitary adenomas (cPAs) commonly related to worse prognosis in patients. Notable progress in understanding of the molecular background of cPAs has been made recently but biology of CCAs remains poorly recognized. Results of our previous study suggested distinct frequency of the known recurrent mutations in CCAs than in sparsely and densely granulated cPAs. Thus, the aim was to determine the prevalence of <i>USP8</i>, <i>USP48</i>, <i>BRAF</i> and <i>TP53</i> variants in a relatively large retrospective group of patients diagnosed with CCA.</p> Methods <p>DNA was isolated from formalin-fixed and paraffin-embedded tissue of 29 CCAs (14 clinically functioning and 15 nonfunctioning). Sanger sequencing was used for the identification of <i>USP8</i>, <i>USP48</i>, <i>BRAF</i> hotspot variants, while semiconductor sequencing with Ion AmpliSeq TP53 Panel was used for analysis of <i>TP53</i> sequence.</p> Results <p><i>USP8</i> variants were found in 2 CCA patients with Cushing’s disease (CD), whereas 3 <i>TP53</i> variants were identified in 1 CCA patient with CD and 2 patients with clinically nonfunctioning CCAs. <i>USP8</i> variants are less frequent in clinically functioning CCAs than functioning sparsely and densely granulated corticotroph tumors (<i>p</i> = 0.0271). <i>TP53</i> variants are more common in CCAs as compared to other histological subtypes (<i>p</i> = 0.0164). One <i>BRAF</i> V600E variant and no <i>USP48</i> variant were found.</p> Conclusion <p>CCAs have slightly distinct mutational profile then other histological subtypes of cPAs. Since clinical relevance of <i>TP53</i> variants in corticotroph tumors was already documented, testing toward <i>TP53</i> sequence changes in patients with CCAs should be considered.</p>

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USP8, USP48, BRAF and TP53 mutations in crooke cell adenoma

  • 期刊论文

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  • 发表日期：

    2025年10月5日

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  • Paulina Kober,
  • Magdalena Szczepaniak,
  • Monika Pękul,
  • Natalia Rusetska,
  • Beata J. Mossakowska,
  • Artur Kowalik,
  • Maria Maksymowicz,
  • Grzegorz Zieliński,
  • Jacek Kunicki,
  • Mateusz Bujko

摘要

Purpose

Crooke cell adenomas (CCAs) are rare histological subtype of corticotroph pituitary adenomas (cPAs) commonly related to worse prognosis in patients. Notable progress in understanding of the molecular background of cPAs has been made recently but biology of CCAs remains poorly recognized. Results of our previous study suggested distinct frequency of the known recurrent mutations in CCAs than in sparsely and densely granulated cPAs. Thus, the aim was to determine the prevalence of USP8, USP48, BRAF and TP53 variants in a relatively large retrospective group of patients diagnosed with CCA.

Methods

DNA was isolated from formalin-fixed and paraffin-embedded tissue of 29 CCAs (14 clinically functioning and 15 nonfunctioning). Sanger sequencing was used for the identification of USP8, USP48, BRAF hotspot variants, while semiconductor sequencing with Ion AmpliSeq TP53 Panel was used for analysis of TP53 sequence.

Results

USP8 variants were found in 2 CCA patients with Cushing’s disease (CD), whereas 3 TP53 variants were identified in 1 CCA patient with CD and 2 patients with clinically nonfunctioning CCAs. USP8 variants are less frequent in clinically functioning CCAs than functioning sparsely and densely granulated corticotroph tumors (p = 0.0271). TP53 variants are more common in CCAs as compared to other histological subtypes (p = 0.0164). One BRAF V600E variant and no USP48 variant were found.

Conclusion

CCAs have slightly distinct mutational profile then other histological subtypes of cPAs. Since clinical relevance of TP53 variants in corticotroph tumors was already documented, testing toward TP53 sequence changes in patients with CCAs should be considered.