Reference Detail

Ref Type

Journal Article

PMID

(32236518)

Authors

Nishimura S, Yashiro M, Sera T, Yamamoto Y, Kushitani Y, Sugimoto A, Kushiyama S, Togano S, Kuroda K, Okuno T, Murakami Y, Ohira M

Title

Serine threonine kinase 11/liver kinase B1 mutation in sporadic scirrhous-type gastric cancer cells.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Carcinogenesis	41	11	2020 Nov 13	1616-1623	Carcinogenesis

URL

Abstract Text

Scirrhous-type gastric carcinoma (SGC), which is characterized by the rapid proliferation of cancer cells accompanied by extensive fibrosis, shows extremely poor survival. A reason for the poor prognosis of SGC is that the driver gene responsible for SGC has not been identified. To identify the characteristic driver gene of SGC, we examined the genomic landscape of six human SGC cell lines of OCUM-1, OCUM-2M, OCUM-8, OCUM-9, OCUM-12 and OCUM-14, using multiplex gene panel testing by next-generation sequencing. In this study, the non-synonymous mutations of serine threonine kinase 11/liver kinase B1 (STK11/LKB1) gene were detected in OCUM-12, OCUM-2M and OCUM-14 among the six SGC cell lines. Capillary sequencing analysis confirmed the non-sense or missense mutation of STK11/LKB1 in the three cell lines. Western blot analysis showed that LKB1 expression was decreased in OCUM-12 cells and OCUM-14 cells harboring STK11/LKB1 mutation. The mammalian target of rapamycin (mTOR) inhibitor significantly inhibited the proliferation of OCUM-12 and OCUM-14 cells. The correlations between STK11/LKB1 expression and clinicopathologic features of gastric cancer were examined using 708 primary gastric carcinomas by immunochemical study. The low STK11/LKB1 expression group was significantly associated with SGC, high invasion depth and frequent nodal involvement, in compared with the high STK11/LKB1 expression group. Collectively, our study demonstrated that STK11/LKB1 mutation might be responsible for the progression of SGC, and suggested that mTOR signaling by STK11/LKB1 mutation might be one of therapeutic targets for patients with SGC.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance
PBRM1	F1354C	missense	unknown	PBRM1 F1354C does not lie within any known functional domains of the Pbrm1 protein (UniProt.org). F1354C has been identified in sequencing studies (PMID: 32236518), but has not been biochemically characterized and therefore, its effect on Pbrm1 protein function is unknown (PubMed, Jan 2025).
STK11	Y253*	nonsense	loss of function - predicted	STK11 Y253* results in a premature truncation of the Stk11 protein at amino acid 253 of 433 (UniProt.org). Y253* results in reduced Stk11 protein expression in cultured cells (PMID: 32236518), and due to the effects of other truncation mutations downstream of Y253 (PMID: 23612973), is predicted to lead to a loss of Stk11 protein function.

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
STK11 Y253* STK11 dec exp	stomach carcinoma	predicted - sensitive	Sirolimus	Preclinical - Cell culture	Actionable	In a preclinical study, Rapamune (sirolimus) suppressed the growth of gastric carcinoma cells harboring STK11 Y253* with decreased Stk11 protein expression in culture (PMID: 32236518).	32236518