Alternative Lengthening of Telomeres (ALT) and Telomerase Reverse Transcriptase Promoter Methylation in Recurrent Adult and Primary Pediatric Pituitary Neuroendocrine Tumors

Alzoubi, Hiba; Minasi, Simone; Gianno, Francesca; Antonelli, Manila; Belardinilli, Francesca; Giangaspero, Felice; Jaffrain-Rea, Marie Lise; Buttarelli, Francesca Romana

doi:10.1007/s12022-021-09702-0

Cited by 4 publications

(3 citation statements)

References 64 publications

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“…Other molecular markers include ATRX , revealing a diffuse nuclear immunoreactivity; diffuse EGFR staining with some membranous enhancement, and negative BRAF V600E staining. In addition (data not shown), immunostaining for pituitary hormones was negative as already observed at first surgery, the tumor presented an unmethylated pattern of the MGMT promoter and, as previously reported, no telomerase abnormalities [ 24 ].…”

Section: Figuresupporting

confidence: 77%

Immunotherapy for Aggressive and Metastatic Pituitary Neuroendocrine Tumors (PitNETs): State-of-the Art

Feola

Carbonara

Verrico

et al. 2022

Cancers

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Background: Aggressive and metastatic PitNETs are challenging conditions. Immune checkpoint inhibitors (ICIs) are currently considered in cases resistant to temozolomide (TMZ). However, clinical experience is essentially limited to case reports, with variable outcomes. Material and Methods: The effects of ICIs on 12 aggressive/metastatic PitNETs from the literature were reviewed and analyzed according to tumor characteristics, with the additional description of a silent-Pit1 metastatic tumor responding to pembrolizumab. Results: Most cases were metastatic (10/13: 6 corticotroph, 3 lactotroph, 1 silent Pit1); 3 were aggressive (2 corticotroph, 1 lactotroph). ICIS was used either as monotherapy or in combination. At last follow-up on ICI, a complete response (CR) was present in 3 cases and a partial response (PR) in 2 cases (4/5 metastatic). One sustained stable disease (SD) was reported. Progressive disease (PD) was observed in 7 cases, 3 of them after initial SD (n = 1) or PR (n = 3), with 2 reported deaths. PDL1 expression was studied in 10 cases and was high (>95%) in 2 Pit1-derived metastatic PitNETs (1 CR and 1 remarkable PR) but absent/low (<1%) in the remaining cases (including 1 CP and 2 PR). Elevated tumor mutation burden could be informative in corticotroph PitNETs, especially in mismatch repair-deficient tumors. Conclusion: Significant benefits from ICIs were documented in about half of TMZ-resistant PitNETS. High PDL1 expression was associated with remarkable responses but may be dispensable. Based on their acceptable tolerance and awaiting recognized predictors of response, ICIs may be considered a valuable option for such patients.

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Section: Figuresupporting

confidence: 77%

Immunotherapy for Aggressive and Metastatic Pituitary Neuroendocrine Tumors (PitNETs): State-of-the Art

Feola

Carbonara

Verrico

et al. 2022

Cancers

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“…CCND2 and DAPK1 regulate the cell cycle and TIMP2 regulates extracellular matrix homeostasis [56,57]. ZNF676 plays a role in telomere homeostasis but the involvement of telomere dysregulation in PitNETs pathogenesis remains debated [58,59]. In another study, bulk RNA-seq reveals the downregulation of secreted frizzled-related protein 2 (SFRP2) in invasive corticotroph PitNETs [60].…”

Section: Corticotroph Pitnetsmentioning

confidence: 99%

Transcriptomic Profiles of Normal Pituitary Cells and Pituitary Neuroendocrine Tumor Cells

Osorio

Jung

et al. 2022

Cancers

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The pituitary gland is one of the most cellularly diverse regions of the brain. Recent advancements in transcriptomic biology, such as single-cell RNA sequencing, bring an unprecedented glimpse into the molecular composition of the pituitary, both in its normal physiological state and in disease. Deciphering the normal pituitary transcriptomic signatures provides a better insight into the ontological origin and development of five types of endocrine cells, a process involving complex cascades of transcription factors that are still being established. In parallel with these observations about normal pituitary development, recent transcriptomic findings on pituitary neuroendocrine tumors (PitNETs) demonstrate both preservations and changes in transcription factor expression patterns compared to those seen during gland development. Furthermore, recent studies also identify differentially expressed genes that drive various tumor behaviors, including hormone hypersecretion and tumor aggression. Understanding the comprehensive multiomic profiles of PitNETs is essential in developing molecular profile-based therapies for PitNETs not curable with current treatment modalities and could eventually help align PitNETs with the breakthroughs being made in applying precision medicine to other tumors.

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“…In some reports, they were described in both primary tumour and metastasis, while in others, only in metastasis [17,69,72]. Strong ATRX immunopositivity was found in the majority of corticotroph tumours, and a lack of nuclear ATRX immunostaining was observed in several cases of corticotroph tumours carrying ATRX variants [17,72,73].…”

Section: Atrx and Daxxmentioning

confidence: 99%

An Update on the Genetic Drivers of Corticotroph Tumorigenesis

Hernández-Ramírez,

Perez-Rivas,

Theodoropoulou

et al. 2024

Exp Clin Endocrinol Diabetes

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Alternative Lengthening of Telomeres (ALT) and Telomerase Reverse Transcriptase Promoter Methylation in Recurrent Adult and Primary Pediatric Pituitary Neuroendocrine Tumors

Cited by 4 publications

References 64 publications

Immunotherapy for Aggressive and Metastatic Pituitary Neuroendocrine Tumors (PitNETs): State-of-the Art

Immunotherapy for Aggressive and Metastatic Pituitary Neuroendocrine Tumors (PitNETs): State-of-the Art

Transcriptomic Profiles of Normal Pituitary Cells and Pituitary Neuroendocrine Tumor Cells

An Update on the Genetic Drivers of Corticotroph Tumorigenesis

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