Hotspots of Somatic Genetic Variation in Pituitary Neuroendocrine Tumors
The most common genetic drivers of pituitary neuroendocrine tumors (PitNETs) lie within mutational hotspots, which are genomic regions where variants tend to cluster. Some of these hotspot defects are unique to PitNETs, while others are associated with additional neoplasms. Hotspot variants in <i...
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MDPI AG
2023-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/23/5685 |
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| author | Mariana Torres-Morán Alexa L. Franco-Álvarez Rosa G. Rebollar-Vega Laura C. Hernández-Ramírez |
| author_facet | Mariana Torres-Morán Alexa L. Franco-Álvarez Rosa G. Rebollar-Vega Laura C. Hernández-Ramírez |
| author_sort | Mariana Torres-Morán |
| collection | DOAJ |
| description | The most common genetic drivers of pituitary neuroendocrine tumors (PitNETs) lie within mutational hotspots, which are genomic regions where variants tend to cluster. Some of these hotspot defects are unique to PitNETs, while others are associated with additional neoplasms. Hotspot variants in <i>GNAS</i> and <i>USP8</i> are the most common genetic causes of acromegaly and Cushing’s disease, respectively. Although it has been proposed that these genetic defects could define specific clinical phenotypes, results are highly variable among studies. In contrast, <i>DICER1</i> hotspot variants are associated with a familial syndrome of cancer predisposition, and only exceptionally occur as somatic changes. A small number of non-<i>USP8</i>-driven corticotropinomas are due to somatic hotspot variants in <i>USP48</i> or <i>BRAF</i>; the latter is a well-known mutational hotspot in cancer. Finally, somatic variants affecting a hotspot in <i>SF3B1</i> have been associated with multiple cancers and, more recently, with prolactinomas. Since the associations of <i>BRAF</i>, <i>USP48</i>, and <i>SF3B1</i> hotspot variants with PitNETs are very recent, their effects on clinical phenotypes are still unknown. Further research is required to fully define the role of these genetic defects as disease biomarkers and therapeutic targets. |
| first_indexed | 2024-03-09T01:53:41Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T01:53:41Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-404c5ea68fc04e128476773a17ec6ec82023-12-08T15:12:56ZengMDPI AGCancers2072-66942023-12-011523568510.3390/cancers15235685Hotspots of Somatic Genetic Variation in Pituitary Neuroendocrine TumorsMariana Torres-Morán0Alexa L. Franco-Álvarez1Rosa G. Rebollar-Vega2Laura C. Hernández-Ramírez3Red de Apoyo a la Investigación, Coordinación de la Investigación Científica, Universidad Nacional Autónoma de México e Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, MexicoRed de Apoyo a la Investigación, Coordinación de la Investigación Científica, Universidad Nacional Autónoma de México e Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, MexicoRed de Apoyo a la Investigación, Coordinación de la Investigación Científica, Universidad Nacional Autónoma de México e Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, MexicoRed de Apoyo a la Investigación, Coordinación de la Investigación Científica, Universidad Nacional Autónoma de México e Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, MexicoThe most common genetic drivers of pituitary neuroendocrine tumors (PitNETs) lie within mutational hotspots, which are genomic regions where variants tend to cluster. Some of these hotspot defects are unique to PitNETs, while others are associated with additional neoplasms. Hotspot variants in <i>GNAS</i> and <i>USP8</i> are the most common genetic causes of acromegaly and Cushing’s disease, respectively. Although it has been proposed that these genetic defects could define specific clinical phenotypes, results are highly variable among studies. In contrast, <i>DICER1</i> hotspot variants are associated with a familial syndrome of cancer predisposition, and only exceptionally occur as somatic changes. A small number of non-<i>USP8</i>-driven corticotropinomas are due to somatic hotspot variants in <i>USP48</i> or <i>BRAF</i>; the latter is a well-known mutational hotspot in cancer. Finally, somatic variants affecting a hotspot in <i>SF3B1</i> have been associated with multiple cancers and, more recently, with prolactinomas. Since the associations of <i>BRAF</i>, <i>USP48</i>, and <i>SF3B1</i> hotspot variants with PitNETs are very recent, their effects on clinical phenotypes are still unknown. Further research is required to fully define the role of these genetic defects as disease biomarkers and therapeutic targets.https://www.mdpi.com/2072-6694/15/23/5685genetic drivermutational hotspotpituitary neuroendocrine tumorsomatic variantdruggable target |
| spellingShingle | Mariana Torres-Morán Alexa L. Franco-Álvarez Rosa G. Rebollar-Vega Laura C. Hernández-Ramírez Hotspots of Somatic Genetic Variation in Pituitary Neuroendocrine Tumors Cancers genetic driver mutational hotspot pituitary neuroendocrine tumor somatic variant druggable target |
| title | Hotspots of Somatic Genetic Variation in Pituitary Neuroendocrine Tumors |
| title_full | Hotspots of Somatic Genetic Variation in Pituitary Neuroendocrine Tumors |
| title_fullStr | Hotspots of Somatic Genetic Variation in Pituitary Neuroendocrine Tumors |
| title_full_unstemmed | Hotspots of Somatic Genetic Variation in Pituitary Neuroendocrine Tumors |
| title_short | Hotspots of Somatic Genetic Variation in Pituitary Neuroendocrine Tumors |
| title_sort | hotspots of somatic genetic variation in pituitary neuroendocrine tumors |
| topic | genetic driver mutational hotspot pituitary neuroendocrine tumor somatic variant druggable target |
| url | https://www.mdpi.com/2072-6694/15/23/5685 |
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