JP-7856963-B2 - A method for classifying colorectal cancer patients into the HCCC group or the LMCC group.

JP7856963B2JP 7856963 B2JP7856963 B2JP 7856963B2JP-7856963-B2

Inventors

石岡千加史
高橋信
大内康太
沖田啓
齋藤辰朗
仲村順子
津矢田明泰

Assignees

国立大学法人東北大学
株式会社理研ジェネシス

Dates

Publication Date: 20260512
Application Date: 20241017
Priority Date: 20190531

Claims (2)

A method for assisting in classifying colorectal cancer patients into the HMCC group or the LMCC group, The step includes determining the methylation state of at least one region selected from the group consisting of regions (i) to (xvi) in the DNA collected from the patient , The aforementioned determination result suggests whether the patient is classified into the HMCC group or the LMCC group. Region (i) is the region of chromosome 2, 207307150–207309004 , and the methylation status in this region is determined based on the detection of methylation of at least one base selected from the group consisting of bases 207307150, 207307490, 207307544, 207307622, 207307732, 207308004, 207308087, 207308375, and 207309003. Region (ii) is the region of chromosome 2, from 241758282 to 241760510 , and the methylation status in this region is determined based on the detection of methylation of at least one base selected from the group consisting of bases 241758282, 241758399, 241758805, 241758901, 241759279, 241759414, 241760025, 241760164, 241760190, and 241760509. Region (iii) is the region of chromosome 3 , from 150802997 to 150805168 , and the methylation status in this region is determined based on the detection of methylation of at least one base selected from the group consisting of bases 150803295, 150803307, 150803666, 150804063, 150804313, 150804490, 150804696, 150804719, and 150805167. Region (iv) is the region of chromosome 4 , positions 141347993 to 141348489 , and the methylation status in this region is determined based on the detection of methylation of at least one base selected from the group consisting of bases 141347993, 141348043, 141348167, and 141348307. Region (v) is the region of chromosome 4 , from 186048714 to 186050048 , and the methylation status in this region is determined based on the detection of methylation of at least one base selected from the group consisting of bases 186048714, 186048907, 186049926, and 186050047. Region (vi) is the region of chromosome 5 , from 17216679 to 17219240 , and the methylation status in this region is determined based on the detection of methylation of at least one base selected from the group consisting of bases 17216679, 17216922, 17217093, 17217877, 17218089, 17218278, 17218308, 17218547, 17218778, 17219020, 17219128, 17219226, and 17219239. Region (vii) is the region of chromosome 6 , from 37663982 to 37664539 , and the methylation status in this region is determined based on the detection of methylation of at least one base selected from the group consisting of bases 37663982, 37664451, and 37664538. Region (viiii) is the region of chromosome 6 , from 39281183 to 39282332 , and the methylation status in this region is determined based on the detection of methylation of at least one base selected from the group consisting of bases 39281183, 39281421, 39281450, 39281541, 39281694, 39282164, and 39282331. Region (ix) is the region of chromosome 7 , from position 42273390 to 42277951 , and the methylation states in this region are 42275601, 42275813, 42275870, 42275872, 42276004, 42276819, 42276848, 42276881, 42276890, The determination is made based on the detection of methylation of at least one base selected from the group consisting of the 42276941st, 42276981st, 42277044th, 42277066th, 42277071st, 42277347th, 42277375th, 42277394th, 42277410th, and 42277807th bases. Region (x) is the region between 13039715 and 13043422 of chromosome 10 , and the methylation status in this region is determined based on the detection of methylation of at least one base selected from the group consisting of bases 13039715, 13041989, 13043313, and 13043421. Region (xi) is the region of chromosome 10 , from 81664401 to 81665076 , and the methylation state in this region is determined based on the detection of methylation of at least one base selected from the group consisting of bases 81664401, 81664567, 81664583, 81664698, 81664955, and 81665075. Region (xii) is the region of chromosome 10 , from 88126287 to 88127189 , and the methylation state in this region is determined based on the detection of methylation of at least one base selected from the group consisting of bases 88126287, 88126291, and 88127188. Region (xiiii) is the region of chromosome 11, from 61595807 to 61596627 , and the methylation state in this region is determined based on the detection of methylation of at least one base selected from the group consisting of bases 61595956, 61596068, 61596307, 61596333, and 61596626. Region (xiv) is the region of chromosome 14 , from 23820337 to 23822266 , and the methylation status in this region is determined based on the detection of methylation of at least one base selected from the group consisting of bases 23820337, 23821149, 23821229, 23821435, 23821445, 23821596, 23821902, 23822017, and 23822265. Region (xv) is the region of chromosome 17 , from position 44895317 to 44896749 , and the methylation state in this region is determined based on the detection of methylation of at least one base selected from the group consisting of bases 44895317, 44896080, 44896147, 44896162, 44896166, 44896168, 44896212, and 44896223. Region (xvi) is the region between chromosome 19, positions 39520228 and 39523159 , and the methylation status in this region is determined based on the detection of methylation of at least one base selected from the group consisting of bases 39520228, 39521931, 39522418, 39522747, 39522944, 39523083, and 39523158 .
A method for classifying a patient into the HMCC group or the LMCC group, wherein the detection result indicates whether the patient is classified into the HMCC group or the LMCC group, by detecting methylation at at least one site selected from the group consisting of the following CpG sites in DNA collected from a colorectal cancer patient. Chromosome 2, positions 207307150, 207307490, 207307544, 207307622, 207307732, 207308004, 207308087 , 207308375, 207309003, 241758282, 241758399, 241758805, 241758901, 241759279, 241759414, 241760025 , 241760164, 241760190 , 241760509, Chromosome 3, positions 150803295, 150803307, 150803666, 150804063, 150804313 , 150804490 , 150804696, 150804719, 150805167, Chromosome 4, positions 141347993, 141348043, 141348167 , 141348307 , 186048714, 186048907 , 186049926, 186050047, Chromosome 5, positions 17216679 , 17216922 , 17217093, 17217877, 17218089, 17218278, 17218308, 17218547, 17218778, 17219020, 17219128, 17219226, 17219239, Chromosome 6, positions 37663982 , 37664451 , 37664538, 39281183, 39281421, 39281450 , 39281541, 39281694 , 39282164 , 39282331, Chromosome 7, positions 4,2275601 , 4,2275813, 4,2275870, 4,2275872, 4,2276004, 4,2276819, 4,2276848 , 4,2276881 , 4,2276890, 4,2276941 , 4,2276981, 4,2277044, 4,2277066, 4,2277071, 4,2277347, 4,2277375, 4,2277394, 4,2277410, 4,2277807 , Chromosome 10, positions 13039715, 13041989 , 13043313 , 13043421, 81664401, 81664567 , 81664583, 81664698 , 81664955, 81665075 , 88126287, 88126291 , 88127188, Chromosome 11, positions 6,1595,956 , 6,159,6068, 6,159,6307, 6,159,6333 , and 6,159,626, Chromosome 14, positions 23820337, 23821149, 23821229, 23821435 , 23821445, 23821596, 23821902 , 23822017 , 23822265, Chromosome 17, positions 44895317 , 44896080, 44896147, 44896162, 44896166, 44896168, 44896212, 44896223 , Bases 39520228, 39521931, 39522418 , 39522747, 39522944, 39523083, and 39523158 of chromosome 19 .

Description

[Cross-reference of related applications] This application claims priority to Japanese Patent Application No. 2019-103299, filed on 31 May 2019 (the entire disclosure thereof is incorporated herein by reference). The present invention relates to a method for testing the sensitivity of colorectal cancer to drug therapy. Colorectal cancer is a general term for cancers that develop in the large intestine (colon, rectum, and anus). Colorectal cancer has a high incidence and mortality rate among cancers, and research into its treatment methods continues. Furthermore, as one attempt in cancer treatment research, "personalized medicine" is being considered to maximize treatment effectiveness and minimize side effects. For example, Patent Document 1 contains 24 genes represented by the following Target IDs: cg01791410, cg01802453, cg02484469, cg02916312, cg03839709, cg05218346, cg07005523, cg01068327, cg07258916, cg01360792, cg09767602, cg11092616, cg12646649, cg13261931, cg16041660, cg16958716, cg1 A method has been described for predicting the response of colorectal cancer patients to cancer drug therapy using anti-EGFR antibodies, using 1188046, cg18412834, cg20012008, cg20265733, cg20339230, cg21787291, cg24792289, and cg27628784 as marker genes, and whether or not the bases at specific positions in these marker genes are methylated (Reference 1, Example 8, etc.). WO2016/060278A1 The graph below summarizes the progression-free survival (PFS) for each group in Example 2.The graph below summarizes the progression-free survival (PFS) for each group in Example 3.The graph shows the progression-free survival (PFS) for each group in 83 cases of advanced or recurrent colorectal cancer with wild-type KRAS gene in Example 4.The graph shows the progression-free survival (PFS) for each group in the 65 cases of wild-type RAS genes in Example 4.The results of DNA methylation analysis around Target ID cg07319626 in the example are shown.The results of DNA methylation analysis around Target ID cg02610058 in the example are shown.The results of DNA methylation analysis around Target ID cg13803214 in the example are shown.The results of DNA methylation analysis around Target ID cg14235416 in the example are shown.The results of DNA methylation analysis around Target ID cg24642320 in the example are shown.The results of DNA methylation analysis around Target ID cg25203704 in the example are shown.The results of DNA methylation analysis around Target ID cg26129310 in the example are shown.The results of DNA methylation analysis around Target ID cg18960642 in the example are shown.The results of DNA methylation analysis around Target ID cg07413609 in the example are shown.The results of DNA methylation analysis around Target ID cg22738219 in the example are shown.The results of DNA methylation analysis around Target ID cg20629468 in the example are shown.The results of DNA methylation analysis around Target ID cg20649951 in the example are shown.The results of DNA methylation analysis around Target ID cg25303599 in the example are shown.The results of DNA methylation analysis around Target ID cg01557297 in the example are shown.The results of DNA methylation analysis around Target ID cg12379948 in the example are shown.The results of DNA methylation analysis around Target ID cg14730085 in the example are shown. (1. Methods for testing the sensitivity of colorectal cancer to drug therapy) The present invention provides a method for testing the sensitivity of drug therapy to colorectal cancer, using methylation at at least one site selected from the group consisting of CpG sites in the following regions (i) to (xvi) in DNA collected from colorectal cancer patients as an indicator: Region (i) Region of chromosome 2, positions 207307150–207309004 (preferably positions 207307490–207308376) Region (ii) Region of chromosome 2, positions 241758282–241760510 (preferably positions 241758805–241760510) Region (iii) Region of chromosome 3, positions 150802997–150805168 (preferably positions 150802997–150804720) Region (iv) Region of chromosome 4, positions 141347993–14134848 Region (v) of chromosome 4, 186048714-1860500 Region (vi) of chromosome 5, 17216679-172192 Region (vii) of chromosome 6, 37663982-3766453 Region (viii) of chromosome 6, 39281183-3928233 Region (ix) of chromosome 7, 42273390-42 Region (x) of chromosome 10, position 277951 (preferably 42275870 to 42276817 Region (xi) of chromosome 10, position 13039715 to 13043422 (preferably 13041989 to 13043422) Region (xi) of chromosome 10, position 81664401 to 81665076 Region (xii) of chromosome 10, position 88126287 to 88127189 (preferably 88126287 to 88126307) Region (xiiii) of chromosome 11, position 61595807 to 6159 Region (xiv) of chromosome 14, position 6627 (preferably 61595807 to 61596334 Region (xv) of chromosome 14, position 23820337 to 23822266 (preferably 23821596 to 23822266 Region (xv) of chromosome 17, position 44895317 to 44896749 (preferably 44895317 to 44896425 Region