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Updated: May 15, 2026
Polysome Fractionation and Analysis of Mammalian Translatomes on a Genome-wide Scale
Published on: May 17, 2014
Transcriptomic classification of prolactinomas and somatotropinomas identifies subtypes with variable resistance to
Fabio Bioletto1,2, Nesrine Benanteur1, Maria Francesca Birtolo1,3
1CNRS UMR8104, INSERM U1016, Institut Cochin, Université Paris Cité, Paris 75014, France.
Objective:
Dopamine agonists and somatostatin analogs are commonly used in prolactinomas and somatotropinomas. Response to these therapies is heterogeneous. Whether resistance is linked to specific tumor subtypes or to shared mechanisms of resistance is not known. The aim was to explore distinct molecular subtypes of prolactinomas and somatotropinomas and their association with response to treatment.
Methods:
The transcriptome of 46 prolactinomas and 58 somatotropinomas was analyzed. Unsupervised classifications were generated and tested for association with histological and clinical data, including response to treatment.
Results:
Four subtypes of prolactinomas were identified, with variable sensitivity to dopamine agonists (P < 10-4). Sensitive tumors accumulated in the subgroup with the highest DRD2 expression, while resistant tumors accumulated in the 3 remaining ones, enriched in genes related to cAMP metabolism, to mitochondrial and ribosomal activity, and to immunity, respectively. Sparsely granulated somatotropinomas (N = 16) presented a separated molecular entity, mixing tumors resistant and sensitive to somatostatin analogs. The remaining somatotropinomas were classified into 5 subtypes, with variable sensitivity to somatostatin analogs (P < 10-4). Sensitive tumors accumulated in 3 subgroups, characterized by GNAS somatic mutation, PIT1 and SF1 coexpression, and the stem-cell marker SOX2 expression, respectively. Resistant tumors accumulated in the 2 remaining ones, enriched in genes related to cell cycle and to mesenchymal differentiation, respectively. Somatostatin receptor 2 (SSTR2) expression was associated with response to somatostatin analogs in sparsely granulated somatotropinomas (P = .022), but not in other somatotropinomas (P = .923).
Conclusions:
Prolactinomas and somatotropinomas were classified into distinct transcriptomic groups. Resistance to medical therapies was linked to distinct tumor subtypes, suggesting distinct mechanisms of resistance.
Insights
Molecular subtypes of prolactinomas and somatotropinomas influence treatment response. Resistance to dopamine agonists and somatostatin analogs is linked to specific tumor subtypes, indicating varied resistance mechanisms.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Prolactinomas and somatotropinomas are common pituitary tumors.
- Treatment response to dopamine agonists and somatostatin analogs is variable.
- The molecular basis for treatment resistance remains unclear.
Purpose of the Study:
- To classify prolactinomas and somatotropinomas into distinct molecular subtypes.
- To investigate the association between molecular subtypes and treatment response.
Main Methods:
- Transcriptome analysis of 46 prolactinomas and 58 somatotropinomas.
- Unsupervised classification to identify molecular subtypes.
- Correlation of subtypes with histological and clinical data, including treatment response.
Main Results:
- Four prolactinoma subtypes showed differential sensitivity to dopamine agonists, linked to DRD2 expression and immune/metabolic gene enrichment.
- Sparsely granulated somatotropinomas formed a distinct molecular group.
- Five somatotropinoma subtypes exhibited variable sensitivity to somatostatin analogs, associated with GNAS mutations, PIT1/SF1 coexpression, SOX2, cell cycle, or mesenchymal genes.
- SSTR2 expression correlated with treatment response in sparsely granulated somatotropinomas.
Conclusions:
- Prolactinomas and somatotropinomas can be classified into distinct transcriptomic subtypes.
- Treatment resistance in these tumors is associated with specific molecular subtypes.
- These findings suggest diverse mechanisms underlying therapeutic resistance.
