Molecular profiling of signet-ring-cell carcinoma (SRCC) from the stomach and colon reveals potential new therapeutic targets.
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
23
12
2021
accepted:
06
05
2022
revised:
04
05
2022
pubmed:
27
5
2022
medline:
29
6
2022
entrez:
26
5
2022
Statut:
ppublish
Résumé
Signet ring cell carcinoma (SRCC) is rare: about 10% of gastric cancer (GC) and 1% of colorectal cancer (CRC). SRCC is associated with poor prognosis, however the underlying molecular characteristics are unknown. SRCCs were analyzed using NGS, immunohistochemistry, and in situ hybridization. Tumor mutational burden (TMB) was calculated based on somatic nonsynonymous missense mutations, and microsatellite instability (MSI) was evaluated by NGS of known MSI loci. A total of 8500 CRC and 1100 GC were screened. Seventy-six SRCC were identified from the CRC cohort (<1%) and 98 from the GC cohort (9%). The most frequently mutated genes in CRC-SRCC were TP53 (47%), ARID1A (26%), APC (25%); in GC-SRCC were TP53 (42%), ARID1A (27%), CDH1 (11%). When compared to non-SRCC histology (N = 3522), CRC-SRCC (N = 37) more frequently had mutations in BRCA1 (11% vs 1%, P < 0.001) and less frequently mutations in APC (19% vs 78%, P < 0.001), KRAS (22% vs 51%, P = 0.001) and TP53 (47% vs 73%, P = 0.001). Among the GC cohort, SRCC (N = 54) had a higher frequency of mutations in CDH1, BAP1, and ERBB2, compared to non-SRCC (N = 540). Our data suggest that SRCCs harbor a similar molecular profile, regardless of the tumor location. Tailored therapy may become available for these patients.
Identifiants
pubmed: 35618879
doi: 10.1038/s41388-022-02350-6
pii: 10.1038/s41388-022-02350-6
pmc: PMC9457205
mid: NIHMS1828799
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3455-3460Subventions
Organisme : NCI NIH HHS
ID : P30 CA014089
Pays : United States
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
Références
Cancers (Basel). 2020 Jun 11;12(6):
pubmed: 32545410
Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820960746
pubmed: 32945232
Ann Surg. 2017 May;265(5):946-953
pubmed: 27232252
PLoS One. 2017 May 9;12(5):e0176637
pubmed: 28486494
Ann Surg Oncol. 2012 Sep;19(9):2814-21
pubmed: 22476818
Sci Rep. 2020 Aug 24;10(1):14126
pubmed: 32839528
Anticancer Res. 2017 Jul;37(7):3817-3823
pubmed: 28668881
Am J Surg. 2007 Sep;194(3):294-8
pubmed: 17693269
Ann Surg. 2009 Dec;250(6):878-87
pubmed: 19855261
J Clin Oncol. 2020 Jan 1;38(1):1-10
pubmed: 31682550
Br J Cancer. 2019 Sep;121(6):505-510
pubmed: 31406299
J Clin Oncol. 2012 Oct 1;30(28):3493-8
pubmed: 22927530
Gastric Cancer. 2019 Jan;22(1):1-9
pubmed: 30167905
Ann Surg Oncol. 2015 Apr;22(4):1226-1235
pubmed: 25326395
Am J Gastroenterol. 1996 Oct;91(10):2195-9
pubmed: 8855747
Histopathology. 2020 Jan;76(2):182-188
pubmed: 31433515
Oncologist. 2019 Mar;24(3):319-326
pubmed: 30018131
Ann Surg Oncol. 2014 May;21(5):1678-85
pubmed: 24394986
Mayo Clin Proc. 2010 Dec;85(12):1130-6
pubmed: 21123640
N Engl J Med. 2020 Dec 3;383(23):2207-2218
pubmed: 33264544
Arch Pathol Lab Med. 2004 Jul;128(7):765-70
pubmed: 15214826
Gastric Cancer. 2014 Jan;17(1):43-53
pubmed: 23389081
Updates Surg. 2018 Jun;70(2):167-171
pubmed: 29948660
J Hematol Oncol. 2015 May 15;8:52
pubmed: 25976888
J Cancer Res Clin Oncol. 2016 Nov;142(11):2357-66
pubmed: 27573386
Ann Surg. 2013 Nov;258(5):775-82; discussion 782-3
pubmed: 23989057
PLoS One. 2016 Sep 01;11(9):e0162088
pubmed: 27583684
Cancers (Basel). 2022 Mar 09;14(6):
pubmed: 35326540
Front Oncol. 2021 Oct 11;11:662055
pubmed: 34707985
World J Gastroenterol. 2015 Oct 28;21(40):11428-38
pubmed: 26523107
Br J Cancer. 2017 Jul 11;117(2):203-209
pubmed: 28595259
Nature. 2012 Jul 18;487(7407):330-7
pubmed: 22810696
Oncotarget. 2017 Jun 13;8(24):38850-38862
pubmed: 28418918
Dis Colon Rectum. 2008 Jan;51(1):50-5
pubmed: 18030531
Sci Rep. 2016 Jul 06;6:26313
pubmed: 27381549
Cancer Cell. 2018 Jan 8;33(1):125-136.e3
pubmed: 29316426
Int J Cancer. 2015 Jan 15;136(2):333-9
pubmed: 24841868
Ann Oncol. 2020 Sep;31(9):1135-1147
pubmed: 32512040
Exp Mol Med. 2021 Feb;53(2):223-234
pubmed: 33547412
Future Oncol. 2020 Jun;16(17):1161-1163
pubmed: 32351144