【正文】 測試劑盒及其檢測方法 廣州達健生物科技有限公司 CN202310330990 用于檢測結(jié)直腸癌 PIK3CA基因熱點突變位點的試劑盒 杭州艾迪康醫(yī)學檢驗中心有限公司 CN202310234133 一種檢測人 PIK3CA基因突變的方法和試劑盒 蘇州科貝生物技術有限公司 CN202310608500 1. 項目背景 10 cancer % PIK3CA mutation Sample source (primary tissue vs cancer cell line) Exon mutated Functional domain Reference Liver (26/73) Primary 9 and 20 Helical and kinase Lee et al (2023) Total liver 36% (26/73) Breast (4/12) Cell lines 9 and 20 Helical and kinase Bachman et al(2023) Breast (9/42) Primary 1, 9 and 20 p85, helical and kinase Bachman et al(2023) Breast (13/72) Primary 9 and 20 Helical and kinase Levine et al(2023) Breast (28/70) Primary 6, 7, 9 and 20 C2, helical and kinase Campbell et al(2023) Breast (19/92) Primary 9 and 20 Helical and kinase Wu et al (2023a) Breast (1/12) Primary 20 kinase Samuels et al(2023) Breast (5/15) Cell lines 9 and 20 Helical and kinase Wu et al (2023a) Breast (25/93) Primary 9 and 20 Helical and kinase Lee et al (2023) Breast (14/50) Cell lines 1, 9 and 20 p85, helical and kinase Saal et al (2023) Breast (77/292) Primary 1, 4, 7, 9, 13, 18, 20 p85, C2, helical and kinase Saal et al (2023) Total breast 26% (195/750) Colon (74/234) Primary 1, 2, 4, 7, 9, 18 and 20 P85, C2, helical and Kinase Samuels et al(2023) Colon (14/103) Primary 9 and 20 Helical and kinase Velho et al(2023) Colon (6/32) Primary 9 and 20 Helical and kinase Campbell et al(2023) Total colon 25% (94/369) 2. 臨床意義 突變率 11 Ovarian (24/198) Primary 9 and 20 Helical and kinase Levine et al(2023) Ovarian (11/182) Primary 9 and 20 Helical and kinase Campbell et al(2023) Total ovarian 9% (35/380) Gastric (3/12) Primary 18 and 20 Kinase Samuels et al(2023) Gastric (5/47) Primary 9 and 20 Helical and kinase Velho et al(2023) Gastric (12/185) Primary 9 and 20 Helical and kinase Lee et al (2023) Gastric (4/94) Primary 9 and 20 Helical and kinase Li et al (2023) Total gastric 7% (24/338) Brain (4/15) Primary 4, 5 and 13 C2 and helical Samuels et al(2023) Brain (13/285) Primary 9 and 20 Helical and kinase Broderick et al(2023) Total brain 6% (17/300) Lung (3/229) Primary 9 and 20 Helical and kinase Lee et al (2023) Lung (1/24) Primary 9 Helical Samuels et al(2023) Total lung 2% (4/253) Leukaemia (1/88) Primary 9 Helical Lee et al (2023) Total leukaemia 1% (1/88) Total cancers reported 15% (382/2551) [*] 2. 臨床意義 突變率 12 藥物 檢測項目 檢測意義 易瑞沙 特羅凱 EGFR基因突變 預測療效 KRAS基因突變 預測療效 西妥昔單抗 帕尼單抗 KRAS基因突變 預測療效 BRAF基因突變 預測療效 威羅菲尼 BRAF基因突變 預測療效 易瑞沙 特羅凱 西妥昔單抗 帕尼單抗 PIK3CA基因突變 耐藥相關 2. 臨床意義 耐藥 13 ① PI3K作為 EGFR下游信號分子被激活，可導致腫瘤細胞對 EGFRTKI藥物的耐藥，例如 PIK3CA基因的突變可導致 西妥昔單抗（愛必妥），帕尼單抗（維克替比）對轉(zhuǎn)移性結(jié)直腸癌治療的耐受，導致吉非替尼，厄洛替尼對非小細胞肺癌和食道癌晚期患者的治療耐受 [14]。 KRAS，BRAF， PIK3CA任何一個或多個突變對個體化靶向藥物 西妥昔單抗（愛必妥） ， 帕尼單抗（維克替比） 治療無效，全部為野生型治療有效 [4]。 2. 臨床意義 耐藥 14 COSMIC ID NM AA Change 突變率 775 G 80% Common mutations 776 T 760 A 763 A 765 T 15 ? PIK3CA mutation or gene amplification was detected in % of all ovarian cancers and 45% of the endometrioid and clear cell subtypes, and E542K, E545K, E545D, H1047R and H1047L mutations were detected [7]. ? PIK3CA E542K, E545K, and E545D mutation in exon 9, H1047R and H1047L mutation in exon 20 are the mon mutations, and may be associated with the efficacy of EGFRTKI therapy [89]. ? Most of the mutations occur at two hot spot