Multiregion WES of metastatic pancreatic neuroendocrine tumors revealed heterogeneity in genomic alterations, immune microenvironment and evolutionary patterns
© 2024. The Author(s)..
Pancreatic neuroendocrine tumors (PanNETs), though uncommon, have a high likelihood of spreading to other body parts. Previously, the genetic diversity and evolutionary patterns in metastatic PanNETs were not well understood. To investigate this, we performed multiregion sampling whole-exome sequencing (MRS-WES) on samples from 10 patients who had not received prior treatment for metastatic PanNETs. This included 29 primary tumor samples, 31 lymph node metastases, and 15 liver metastases. We used the MSK-MET dataset for survival analysis and validation of our findings. Our research indicates that mutations in the MEN1/DAXX genes might trigger the early stages of PanNET development. We categorized the patients based on the presence (MEN1/DAXXmut, n = 7) or absence (MEN1/DAXXwild, n = 3) of these mutations. Notable differences were observed between the two groups in terms of genetic alterations and clinically relevant mutations, confirmed using the MSK-MET dataset. Notably, patients with mutations in MEN1/DAXX/ATRX genes had a significantly longer median overall survival compared to those without these mutations (median not reached vs. 43.63 months, p = 0.047). Multiplex immunohistochemistry (mIHC) analysis showed a more prominent immunosuppressive environment in metastatic tumors, especially in patients with MEN1/DAXX mutations. These findings imply that MEN1/DAXX mutations lead PanNETs through a unique evolutionary path. The disease's progression pattern indicates that PanNETs can spread early, even before clinical detection, highlighting the importance of identifying biomarkers related to metastasis to guide personalized treatment strategies.
| Errataetall: |
ErratumIn: Cell Commun Signal. 2024 Mar 14;22(1):181. - PMID 38486254 |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:22 |
|---|---|
| Enthalten in: |
Cell communication and signaling : CCS - 22(2024), 1 vom: 06. März, Seite 164 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Jiang, Yu [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Journal Article |
|---|
| Anmerkungen: |
Date Completed 08.03.2024 Date Revised 20.03.2024 published: Electronic ErratumIn: Cell Commun Signal. 2024 Mar 14;22(1):181. - PMID 38486254 Citation Status MEDLINE |
|---|
| doi: |
10.1186/s12964-024-01545-6 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM369386612 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM369386612 | ||
| 003 | DE-627 | ||
| 005 | 20240322000447.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240307s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1186/s12964-024-01545-6 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1339.xml |
| 035 | |a (DE-627)NLM369386612 | ||
| 035 | |a (NLM)38448900 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Jiang, Yu |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Multiregion WES of metastatic pancreatic neuroendocrine tumors revealed heterogeneity in genomic alterations, immune microenvironment and evolutionary patterns |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 08.03.2024 | ||
| 500 | |a Date Revised 20.03.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a ErratumIn: Cell Commun Signal. 2024 Mar 14;22(1):181. - PMID 38486254 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a Pancreatic neuroendocrine tumors (PanNETs), though uncommon, have a high likelihood of spreading to other body parts. Previously, the genetic diversity and evolutionary patterns in metastatic PanNETs were not well understood. To investigate this, we performed multiregion sampling whole-exome sequencing (MRS-WES) on samples from 10 patients who had not received prior treatment for metastatic PanNETs. This included 29 primary tumor samples, 31 lymph node metastases, and 15 liver metastases. We used the MSK-MET dataset for survival analysis and validation of our findings. Our research indicates that mutations in the MEN1/DAXX genes might trigger the early stages of PanNET development. We categorized the patients based on the presence (MEN1/DAXXmut, n = 7) or absence (MEN1/DAXXwild, n = 3) of these mutations. Notable differences were observed between the two groups in terms of genetic alterations and clinically relevant mutations, confirmed using the MSK-MET dataset. Notably, patients with mutations in MEN1/DAXX/ATRX genes had a significantly longer median overall survival compared to those without these mutations (median not reached vs. 43.63 months, p = 0.047). Multiplex immunohistochemistry (mIHC) analysis showed a more prominent immunosuppressive environment in metastatic tumors, especially in patients with MEN1/DAXX mutations. These findings imply that MEN1/DAXX mutations lead PanNETs through a unique evolutionary path. The disease's progression pattern indicates that PanNETs can spread early, even before clinical detection, highlighting the importance of identifying biomarkers related to metastasis to guide personalized treatment strategies | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a MEN1/DAXX | |
| 650 | 4 | |a Multiregion sampling whole-exome sequencing | |
| 650 | 4 | |a Pancreatic neuroendocrine tumors | |
| 700 | 1 | |a Dong, Yi-Han |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Shi-Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Dong-Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Ji-Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Xiao-Ya |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Jia-Bin |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cell communication and signaling : CCS |d 2003 |g 22(2024), 1 vom: 06. März, Seite 164 |w (DE-627)NLM143253794 |x 1478-811X |7 nnns |
| 773 | 1 | 8 | |g volume:22 |g year:2024 |g number:1 |g day:06 |g month:03 |g pages:164 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1186/s12964-024-01545-6 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 22 |j 2024 |e 1 |b 06 |c 03 |h 164 | ||