Molecular profiling of signet-ring-cell carcinoma (SRCC) from the stomach and colon reveals potential new therapeutic targets.

Puccini, Alberto; Poorman, Kelsey; Catalano, Fabio; Seeber, Andreas; Goldberg, Richard M; Salem, Mohamed E; Shields, Anthony F; Berger, Martin D; Battaglin, Francesca; Tokunaga, Ryuma; Naseem, Madiha; Zhang, Wu; Philip, Philip A; Marshall, John L; Korn, W Michael; Lenz, Heinz-Josef (2022). Molecular profiling of signet-ring-cell carcinoma (SRCC) from the stomach and colon reveals potential new therapeutic targets. Oncogene, 41(26), pp. 3455-3460. Springer Nature 10.1038/s41388-022-02350-6

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

UniBE Contributor:

Berger, Martin Dave

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1476-5594

Publisher:

Springer Nature

Language:

English

Submitter:

Rebeka Gerber

Date Deposited:

19 Sep 2022 11:35

Last Modified:

28 May 2023 00:25

Publisher DOI:

10.1038/s41388-022-02350-6

PubMed ID:

35618879

BORIS DOI:

10.48350/172998

URI:

https://boris.unibe.ch/id/eprint/172998

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