NOTCH gene alterations in metastatic colorectal cancer in the Nationwide Cancer Genome Screening Project in Japan (SCRUM-Japan GI-SCREEN)

Kajiwara, Takeshi; Nishina, Tomohiro; Nakasya, Akio; Yamashita, Natsumi; Yamashita, Riu; Nakamura, Yoshiaki; Shiozawa, Manabu; Yuki, Satoshi; Taniguchi, Hiroya; Ohta, Takashi; Esaki, Taito; Shinozaki, Eiji; Takashima, Atsuo; Moriwaki, Toshikazu; Denda, Tadamichi; Ohtsubo, Koushiro; Sunakawa, Yu; Horita, Yuki; Kawakami, Hisato; Kato, Takeshi; Satoh, Taroh; Ando, Koji; Yasui, Hisateru; Goto, Masahiro; Okuyama, Hiroomi; Yamazaki, Kentaro; Yoshino, Takayuki; Hyodo, Ichinosuke

doi:10.1007/s00432-022-04064-4

Cited by 1 publication

(2 citation statements)

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“…The TP53 variant was more commonly observed in left-sided CRC, whereas the KRAS and BRAF variants were more prevalent in right-sided CC. In this study, the NOTCH3 sole variant without the covariant of NOTCH1 or NOTCH2 is an independent favorable prognostic factor [18].…”

Section: Introductionmentioning

confidence: 56%

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Sidedness-Dependent Prognostic Impact of Gene Alterations in Metastatic Colorectal Cancer in the Nationwide Cancer Genome Screening Project in Japan (SCRUM-Japan GI-SCREEN)

Kajiwara,

Nishina,

Yamashita

et al. 2023

Cancers

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The treatment strategies and prognoses of patients with metastatic colorectal cancer (CRC) differ according to the sidedness of the primary tumor. TP53 gain-of-function (GOF) and non-GOF variants have been reported to be differentially associated with prognosis by sidedness. We aimed to evaluate the sidedness-dependent prognostic impact of gene alterations in metastatic CRC. Patients enrolled between April 2017 and March 2019 were included in this study. Those excluded were individuals whose tumor tissues were obtained after chemotherapy and those who were enrolled in the study more than six months after starting first-line chemotherapy. Finally, we assessed 531 patients who underwent complete gene sequencing. The study revealed a significant difference in overall survival between individuals with left-sided CRC (n = 355) and right-sided colon cancer (CC) (n = 176) when considering the TP53 non-GOF variant, KRAS wild-type, NOTCH1 wild-type, NOTCH1 covariant, NOTCH3 sole variant, and MYC amplification. Multivariate analysis on each side revealed that the TP53 GOF and KRAS variants were independent poor prognostic factors for left-sided CRC (p = 0.03 and p < 0.01, respectively), and the TP53 non-GOF variant, BRAF V600E, and MYC amplification for right-sided CC (p < 0.05, p < 0.01, and p = 0.02, respectively). The NOTCH3 sole variant was an independent and favorable prognostic factor for left-sided CRC (p < 0.01). The prognostic significance of gene alterations differed between left-sided CRC and right-sided CC.

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Section: Introductionmentioning

confidence: 56%

“…We defined the TP53 R175H, R248W, R248Q, R249S, R273H, R273L, and R282W variants as GOF and other TP53 variants as non-GOF in our dataset based on previous literature [15]. NOTCH1, NOTCH2, and NOTCH3 variants were classified as sole variants or covariants with other NOTCH variants, based on our previous study [18].…”

Section: Targeted Sequencingmentioning

confidence: 99%