ES2557411T3 - Métodos y composiciones basados en microARN para el diagnóstico y el tratamiento de cánceres sólidos - Google Patents
Métodos y composiciones basados en microARN para el diagnóstico y el tratamiento de cánceres sólidos Download PDFInfo
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- ES2557411T3 ES2557411T3 ES12154342.5T ES12154342T ES2557411T3 ES 2557411 T3 ES2557411 T3 ES 2557411T3 ES 12154342 T ES12154342 T ES 12154342T ES 2557411 T3 ES2557411 T3 ES 2557411T3
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Abstract
Un método para diagnosticar si un sujeto tiene cáncer de estómago, que comprende: medir el nivel de al menos un primer producto génico de miR-25 en una muestra de ensayo del sujeto, en donde una alteración en el nivel del primer producto génico de miR-25 en la muestra de ensayo, en relación al nivel del primer producto génico de miR-25 en una muestra de control, es indicativo de que el sujeto tiene cáncer de estómago.
Description
- let-7a-4
- 4
- let-7b
- 5
- let-7c
- 6
- let-7d
- 7
- let-7d-v1
- 8
- let-7d-v2
-
imagen7 9
- let-7e
- 10
- let-7f-1
- 11
- let-7f-2-1
-
imagen8 12
- let-7f-2-2
- 13
- let-7g
-
imagen9 14
- let-7i
- 15
- miR-1b-1-1
-
imagen10 16
- miR-1b-1-2
- 17
- miR-1b-2
- 18
- miR-1b
- 19
- miR-1d
- 20
- miR-7-1a
-
imagen11 21
- miR-7-1b
- 22
- miR-7-2
-
imagen12 23
- miR-7-3
- 24
- miR-9-1
-
imagen13 25
- miR-9-2
- 26
- miR-9-3
-
imagen14 27
- miR-10a
- 28
- miR-10b
- 29
- miR-15a-2
- 30
- miR-15a
- 31
- miR-15b-1
- 32
- miR-15b-2
- 33
- miR-16-1
- 34
- miR-16-2
- 35
- miR-16-13
- 36
- miR-17
-
imagen15 37
- miR-18
- 38
- miR-18-13
- 39
- miR-19a
- 40
- miR-19a-13
- 41
- miR-19b-1
- 42
- miR-19b-2
- 43
- miR-19b-13
-
imagen16 44
- miR-19b-X
-
imagen17 45
- miR-20 (miR20a)
- 46
- miR-21
- 47
- miR-21-17
- 48
- miR-22
- 49
- miR-23a
- 50
- miR-23b
- 51
- miR-23-19
-
imagen18 52
- miR-24-1
-
imagen19 53
- miR-24-2
- 54
- miR-24-19
- 55
- miR-24-9
-
imagen20 56
- miR-25
-
imagen21 57
- miR-26a
- 58
- miR-26a-1
- 59
- miR-26a-2
- 60
- miR-26b
- 61
- miR-27a
- 62
- miR-27b-1
- 63
- miR-27b-2
-
imagen22 64
- miR-27-19
- 65
- miR-28
- 66
- miR-29a-2
- 67
- miR-29a
- 68
- miR-29b-1
- 69
- miR-29b-2
- 70
- miR-29c
- 71
- miR-30a
- 72
- miR-30b-1
- 73
- miR-30b-2
- 74
- miR-30c
- 75
- miR-30d
-
imagen23 76
- miR-30e
- 77
- miR-31
- 78
- miR-32
- 79
- miR-33b
- 80
- miR-33b-2
-
imagen24 81
- miR-33
- 82
- miR-34-a
- 83
- miR-34-b
- 84
- miR-34-c
- 85
- miR-91-13
- 86
- miR-92-1
- 87
- miR-92-2
- 88
- miR-93-1 (miR93-2)
- 89
- miR-95-4
- 90
- miR-96-7
-
imagen25 91
- miR-97-6 (miR30*)
- 92
- miR-98
- 93
- miR-99b
-
imagen26 94
- miR-99a
-
imagen27 95
- miR-100-1/2
- 96
- miR-100-11
-
imagen28 97
- miR-101-1 /2
-
imagen29 98
- miR-101
- 99
- miR-101-1
- 100
- miR-101-2
- 101
- miR-101-9
- 102
- miR-102-1
- 103
- miR-102-7.1 (miR-102-7.2)
- 104
- miR-103-2
-
imagen30 105
- miR-103-1
- 106
- miR-104-17
-
imagen31 107
- miR-105-1
-
imagen32 108
- miR-105-2
- 109
- miR-106-a
- 110
- miR-106-b
-
imagen33 111
- miR-107
-
imagen34 112
- miR-108-1pequeño
- 113
- miR-108-2pequeño
- 114
- miR-122a-1
- 115
- miR-122a-2
- 116
- miR-123
-
imagen35 117
- miR-124a-1
- 118
- miR-124a-2
- 119
- miR-124a-3
- 120
- miR-124a
-
imagen36 121
- miR-124b
- 122
- miR-125a-1
-
imagen37 123
- miR-125a-2
- 124
- miR-125b-1
- 125
- miR-125b-2
- 126
- miR-126-1
- 127
- miR-126-2
- 128
- miR-127-1
- 129
- miR-127-2
- 130
- miR-128a
-
imagen38 131
- miR-128b
-
imagen39 132
- miR-128
- 133
- miR-129-1
-
imagen40 134
- miR-129-2
- 135
- miR-130a
- 136
- miR-131-1
- 137
- miR-131-3
- 138
- miR-131
- 139
- miR-132-1
-
imagen41 140
- miR-132-2
- 141
- miR-133a-1
- 142
- miR-133a-2
- 143
- miR-133
- 144
- miR-133b
- 145
- miR-133bpequeño
-
imagen42 146
- miR-134-1
- 147
- miR-134-2
- 148
- miR-135a-1
- 149
- miR-135a-2 (miR-135-2)
- 150
- miR-135
- 151
- miR-135b
- 152
- miR-136-1
-
imagen43 153
- miR-136-2
- 154
- miR-137
-
imagen44 155
- miR-138-1
- 156
- miR-138-2
- 157
- miR-138
-
imagen45 158
- miR-139
- 159
- miR-140
- 160
- miR-140as
- 161
- miR-140s
- 162
- miR-141-1
- 163
- miR-141-2
-
imagen46 164
- miR-142
- 165
- miR-143-1
- 166
- miR-143-2
- 167
- miR-144-1
- 168
- miR-144-2
- 169
- miR-145-1
- 170
- miR-145-2
-
imagen47 171
- miR-146-1
- 172
- miR-146-2
- 173
- miR-147
- 174
- miR-148a (miR148)
- 175
- miR-148b
- 176
- miR-148bpequeño
- 177
- miR-149-1
- 178
- miR-149-2
-
imagen48 179
- miR-150-1
- 180
- miR-150-2
- 181
- miR-151
- 182
- miR-151-2
- 183
- miR-152-1
- 184
- miR-152-2
- 185
- miR-153-1-1
- 186
- miR-153-1-2
-
imagen49 187
- miR-153-2-1
- 188
- miR-153-2-2
- 189
- miR-154-1
- 190
- miR-154-2
- 191
- miR-155
- 192
- miR-156 = miR157 = solapamiento con miR-141
- 193
- miR-158pequeño = miR192
- 194
- miR-159-1pequeño
-
imagen50 195
- miR-161pequeño
-
imagen51 196
- miR-163-1bpequeño
-
imagen52 197
- miR-163-3pequeño
- 198
- miR-162
- 199
- miR-175pequeño = miR224
- 200
- miR-177pequeño
- 201
- miR-180pequeño
- 202
- miR-181a
- 203
- miR-181b-1
- 204
- miR-181b-2
- 205
- miR-181c
- 206
- miR-182-as
- 207
- miR-182
- 208
- miR-183
-
imagen53 209
- miR-184-1
- 210
- miR-184-2
- 211
- miR-185-1
- 212
- miR-185-2
- 213
- miR-186-1
-
imagen54 214
- miR-186-2
- 215
- miR-187
- 216
- miR-188-1
- 217
- miR-188-2
-
imagen55 218
- miR-189-1
-
imagen56 219
- miR-189-2
- 220
- miR-190-1
- 221
- miR-190-2
-
imagen57 222
- miR-191-1
-
imagen58 223
- miR-191-2
- 224
- miR-192-2/3
- 225
- miR-192
- 226
- miR-193-1
- 227
- miR-193-2
-
imagen59 228
- miR-194-1
- 229
- miR-194-2
- 230
- miR-195-1
- 231
- miR-195-2
- 232
- miR-196-1
- 233
- miR-196a-1
- 234
- miR-196a-2 (miR-196-2)
- 235
- miR-196
- 236
- miR-196b
- 237
- miR-197
-
imagen60 238
- miR-197-2
-
imagen61 239
- miR-198
- 240
- miR-199a-1
- 241
- miR-199a-2
-
imagen62 242
- miR-199b
- 243
- miR-199s
- 244
- miR-200a
- 245
- miR-200b
- 246
- miR-200c
- 247
- miR-202
- 248
- miR-203
- 249
- miR-204
- 250
- miR-205
-
imagen63 251
- miR-206-1
- 252
- miR-206-2
- 253
- miR-208
-
imagen64 254
- miR-210
-
imagen65 255
- miR-211
-
imagen66 256
- miR-212
- 257
- miR-213-2
- 258
- miR-213
-
imagen67 259
- miR-214
- 260
- miR-215
- 261
- miR-216
- 262
- miR-217
-
imagen68 263
- miR-218-1
- 264
- miR-218-2
-
imagen69 265
- miR-219
- 266
- miR-219-1
- 267
- miR-219-2
-
imagen70 268
- miR-220
- 269
- miR-221
- 270
- miR-222
- 271
- miR-223
- 272
- miR-224
- 273
- Nombre del Precursor
- Secuencia (5’ a 3’)* SEC ID Nº:
- miR-294-1 (chr16)
- 274
- miR-296
- 275
- miR-299
-
imagen71 276
- miR-301
- 277
- miR-302a
- 278
- miR-302b
- 279
- miR-302c
- 280
- miR-302d
- 281
- miR-320
- 282
- miR-321
- 283
- miR-323
- 284
- miR-324
-
imagen72 285
- miR-325
-
imagen73 286
- miR-326
- 287
- miR-328
-
imagen74 288
- miR-330
- 289
- miR-331
- 290
- miR-335
- 291
- miR-337
-
imagen75 292
- miR-338
-
imagen76 293
- miR-339
-
imagen77 294
- miR-340
- 295
- miR-342
- 296
- miR-345
- 297
- miR-346
- 298
- miR-367
- 299
- miR-368
- 300
- miR-369
- 301
- miR-370
- 302
- miR-371
- 303
- miR-372
- 304
- miR-373
- 305
- miR-374
- 306
- miR-hes1
- 307
- miR-hes2
- 308
- miR-hes3
- 309
- * Una secuencia subrayada dentro de una secuencia precursora corresponde a un transcrito de miR procesado maduro (véase Tabla 1b). Algunas secuencias precursoras tienen dos secuencias subrayadas que indican dos miR maduros diferentes que derivan del mismo precursor. Todas las secuencias son humanas.
Tabla 1b-Secuencias de microARN maduro humano.
- Nombre de miARN Maduro
- Secuencia de miARN Maduro (5’ a 3’) SEC ID Nº microARN precursor correspondiente; véase Tabla 1a
- let-7a
- ugagguaguagguuguauaguu 310 let-7a-1; let-7a-2; let-7a-3; let-7a-4
- let-7b
- ugagguaguagguugugugguu 311
- let-7b
- let-7c
- ugagguaguagguuguaugguu 312
- let-7c
- let-7d
- agagguaguagguugcauagu 313 let-7d; let-7d-v1
- let-7e
- ugagguaggagguuguauagu 314
- let-7e
- let-7f
- ugagguaguagauuguauaguu 315 let-7f-1; let-7f-2-1; let-7f-2-2
- let-7g
- ugagguaguaguuuguacagu 316
- let-7g
- let-7i
- ugagguaguaguuugugcu 317
- let-7i
- miR-1
- uggaauguaaagaaguaugua 318 miR-1b; miR-1b-1; miR-1b-2
- miR-7
- uggaagacuagugauuuuguu 319 miR-7-1; miR-7-1a; miR-7-2; miR-7-3
- miR-9
- ucuuugguuaucuagcuguauga 320 miR-9-1; miR-9-2; miR-9-3
- miR-9*
- uaaagcuagauaaccgaaagu 321 miR-9-1; miR-9-2; miR-9-3
- miR-10a
- uacccuguagauccgaauuugug 322
- miR-10a
- miR-10b
- uacccuguagaaccgaauuugu 323
- miR-10b
- miR-15a
- uagcagcacauaaugguuugug 324 miR-15a; miR-15a-2
- miR-15b
- uagcagcacaucaugguuuaca 325
- miR-15b
- miR-16
- uagcagcacguaaauauuggcg 326 miR-16-1; miR-16-2; miR-16-13
- miR-17-5p
- caaagugcuuacagugcagguagu 327 miR-17
- miR-17-3p
- acugcagugaaggcacuugu 328 miR-17
- miR-18
- uaaggugcaucuagugcagaua 329 miR-18; miR-18-13
- miR-19a
- ugugcaaaucuaugcaaaacuga 330 miR-19a; miR-19a-13
- miR-19b
- ugugcaaauccaugcaaaacuga 331 miR-19b-1; miR-19b-2
- miR-20
- uaaagugcuuauagugcaggua 332 miR-20 (miR-20a)
- miR-21
- uagcuuaucagacugauguuga 333 miR-21; miR-21-17
- miR-22
- aagcugccaguugaagaacugu 334
- miR-22
- miR-23a
- aucacauugccagggauuucc 335
- miR-23a
- miR-23b
- aucacauugccagggauuaccac 336
- miR-23b
- miR-24
- uggcucaguucagcaggaacag 337 miR-24-1; miR-24-2; miR-24-19; miR24-9
- miR-25
- cauugcacuugucucggucuga 338
- miR-25
- miR-26a
- uucaaguaauccaggauaggcu 339 miR-26a; miR-26a-1; miR-26a-2
- miR-26b
- uucaaguaauucaggauaggu 340
- miR-26b
- miR-27a
- uucacaguggcuaaguuccgcc 341
- miR-27a
- miR-27b
- uucacaguggcuaaguucug 342 miR-27b-1; miR-27b-2
- miR-28
- aaggagcucacagucuauugag 343
- miR-28
- miR-29a
- cuagcaccaucugaaaucgguu 344 miR-29a-2; miR-29a
- miR-29b
- uagcaccauuugaaaucagu 345 miR-29b-1; miR-29b-2
- miR-29c
- uagcaccauuugaaaucgguua 346
- miR-29c
- miR-30a-5p
- uguaaacauccucgacuggaagc 347 miR-30a
- miR-30a-3p
- cuuucagucggauguuugcagc 348 miR-30a
- miR-30b
- uguaaacauccuacacucagc 349 miR-30b-1; miR-30b-2
- miR-30c
- uguaaacauccuacacucucagc 350
- miR-30c
- miR-30d
- uguaaacauccccgacuggaag 351
- miR-30d
- miR-30e
- uguaaacauccuugacugga 352
- miR-30e
- miR-31
- ggcaagaugcuggcauagcug 353
- miR-31
- miR-32
- uauugcacauuacuaaguugc 354
- miR-32
- miR-33
- gugcauuguaguugcauug 355 miR-33; miR-33b
- miR-34a
- uggcagugucuuagcugguugu 356
- miR-34a
- miR-34b
- aggcagugucauuagcugauug 357
- miR-34b
- miR-34c
- aggcaguguaguuagcugauug 358
- miR-34c
- miR-92
- uauugcacuugucccggccugu 359 miR-92-2; miR-92-1
- miR-93
- aaagugcuguucgugcagguag 360 miR-93-1; miR-93-2
- miR-95
- uucaacggguauuuauugagca 361
- miR-95
- miR-96
- uuuggcacuagcacauuuuugc 362
- miR-96
- miR-98
- ugagguaguaaguuguauuguu 363
- miR-98
- miR-99a
- aacccguagauccgaucuugug 364
- miR-99a
- miR-99b
- cacccguagaaccgaccuugcg 365
- miR-99b
- miR-100
- uacaguacugugauaacugaag 366
- miR-100
- miR-101
- uacaguacugugauaacugaag 367 miR-101-1; miR-101-2
- miR-103
- agcagcauuguacagggcuauga 368 miR-103-1
- miR-105
- ucaaaugcucagacuccugu 369
- miR-105
- miR-106-a
- aaaagugcuuacagugcagguagc 370
- miR-106-a
- miR-106-b
- uaaagugcugacagugcagau 371
- miR-106-b
- miR-107
- agcagcauuguacagggcuauca 372
- miR-107
- miR-122a
- uggagugugacaaugguguuugu 373 miR-122a-1; miR-122a-2
- miR-124a
- uuaaggcacgcggugaaugcca 374 miR-124a-1; miR-124a-2; miR-124a-3
- miR-125a
- ucccugagacccuuuaaccugug 375 miR-125a-1; miR-125a-2
- miR-125b
- ucccugagacccuaacuuguga 376 miR-125b-1; miR-125b-2
- miR-126*
- cauuauuacuuuugguacgcg 377 miR-126-1; miR-126-2
- miR-126
- ucguaccgugaguaauaaugc 378 miR-126-1; miR-126-2
- miR-127
- ucggauccgucugagcuuggcu 379 miR-127-1; miR-127-2
- miR-128a
- ucacagugaaccggucucuuuu 380 miR-128; miR-128a
- miR-128b
- ucacagugaaccggucucuuuc 381
- miR-128b
- miR-129
- cuuuuugcggucugggcuugc 382 miR-129-1; miR-129-2
- miR-130a
- cagugcaauguuaaaagggc 383
- miR-130a
- miR-130b
- cagugcaaugaugaaagggcau 384
- miR-130b
- miR-132
- uaacagucuacagccauggucg 385 miR-132-1
- miR-133a
- uugguccccuucaaccagcugu 386 miR-133a-1; miR-133a-2
- miR-133b
- uugguccccuucaaccagcua 387
- miR-133b
- miR-134
- ugugacugguugaccagaggg 388 miR-134-1; miR-134-2
- miR-135a
- uauggcuuuuuauuccuauguga 389 miR-135a; miR-135a-2 (miR-135-2)
- miR-135b
- uauggcuuuucauuccuaugug 390
- miR-135b
- miR-136
- acuccauuuguuuugaugaugga 391 miR-136-1; miR-136-2
- miR-137
- uauugcuuaagaauacgcguag 392
- miR-137
- miR-138
- agcugguguugugaauc 393 miR-138-1; miR-138-2
- miR-139
- ucuacagugcacgugucu 394
- miR-139
- miR-140
- agugguuuuacccuaugguag 395 miR-140; miR-140as; miR-140s
- miR-141
- aacacugucugguaaagaugg 396 miR-141-1; miR-141-2
- miR-142-3p
- uguaguguuuccuacuuuaugga 397 miR-142
- miR-142-5p
- cauaaaguagaaagcacuac 398 miR-142
- miR-143
- ugagaugaagcacuguagcuca 399 miR-143-1
- miR-144
- uacaguauagaugauguacuag 400 miR-144-1; miR-144-2
- miR-145
- guccaguuuucccaggaaucccuu 401 miR-145-1; miR-145-2
- miR-146
- ugagaacugaauuccauggguu 402 miR-146-1; miR-146-2
- miR-147
- guguguggaaaugcuucugc 403
- miR-147
- miR-148a
- ucagugcacuacagaacuuugu 404 miR-148a (miR-148)
- miR-148b
- ucagugcaucacagaacuuugu 405
- miR-148b
- miR-149
- ucuggcuccgugucuucacucc 406
- miR-149
- miR-150
- ucucccaacccuuguaccagug 407 miR-150-1; miR-150-2
- miR-151
- acuagacugaagcuccuugagg 408
- miR-151
- miR-152
- ucagugcaugacagaacuugg 409 miR-152-1; miR-152-2
- miR-153
- uugcauagucacaaaaguga 410 miR-153-1-1; miR-153-1-2; miR-153-21; miR-153-2-2
- miR-154
- uagguuauccguguugccuucg 411 miR-154-1; miR-154-2
- miR-154*
- aaucauacacgguugaccuauu 412 miR-154-1; miR-154-2
- miR-155
- uuaaugcuaaucgugauagggg 413
- miR-155
- miR-181a
- aacauucaacgcugucggugagu 414
- miR-181a
- miR-181b
- aacauucauugcugucgguggguu 415 miR-181b-1; miR-181b-2
- miR-181c
- aacauucaaccugucggugagu 416
- miR-181c
- miR-182
- uuuggcaaugguagaacucaca 417 miR-182; miR-182as
- miR-182*
- ugguucuagacuugccaacua 418 miR-182; miR-182as
- miR-183
- uauggcacugguagaauucacug 419
- miR-183
- miR-184
- uggacggagaacugauaagggu 420 miR-184-1; miR-184-2
- miR-185
- uggagagaaaggcaguuc 421 miR-185-1; miR-185-2
- miR-186
- caaagaauucuccuuuugggcuu 422 miR-186-1; miR-186-2
- miR-187
- ucgugucuuguguugcagccg 423
- miR-187
- miR-188
- caucccuugcaugguggagggu 424
- miR-188
- miR-189
- gugccuacugagcugauaucagu 425 miR-189-1; miR-189-2
- miR-190
- ugauauguuugauauauuaggu 426 miR-190-1; miR-190-2
- miR-191
- caacggaaucccaaaagcagcu 427 miR-191-1; miR-191-2
- miR-192
- cugaccuaugaauugacagcc 428
- miR-192
- miR-193
- aacuggccuacaaagucccag 429 miR-193-1; miR-193-2
- miR-194
- uguaacagcaacuccaugugga 430 miR-194-1; miR-194-2
- miR-195
- uagcagcacagaaauauuggc 431 miR-195-1; miR-195-2
- miR-196a
- uagguaguuucauguuguugg 432 miR-196a; miR-196a-2 (miR196-2)
- miR-196b
- uagguaguuuccuguugg 433
- miR-196b
- miR-197
- uucaccaccuucuccacccagc 434
- miR-197
- miR-198
- gguccagaggggagauagg 435
- miR-198
- miR-199a
- cccaguguucagacuaccuguuc 436 miR-199a-1; miR-199a-2
- miR-199a*
- uacaguagucugcacauugguu 437 miR-199a-1; miR-199a-2; miR-199s; miR-199b
- miR-199b
- cccaguguuuagacuaucuguuc 438
- miR-199b
- miR-200a
- uaacacugucugguaacgaugu 439
- miR-200a
- miR-200b
- cucuaauacugccugguaaugaug 440
- miR-200b
- miR-200c
- aauacugccggguaaugaugga 441
- miR-200c
- miR-202
- agagguauagggcaugggaaga 442
- miR-202
- miR-203
- gugaaauguuuaggaccacuag 443
- miR-203
- miR-204
- uucccuuugucauccuaugccu 444
- miR-204
- miR-205
- uccuucauuccaccggagucug 445
- miR-205
- miR-206
- uggaauguaaggaagugugugg 446 miR-206-1; miR-206-2
- miR-208
- auaagacgagcaaaaagcuugu 447
- miR-208
- miR-210
- cugugcgugugacagcggcug 448
- miR-210
- miR-211
- uucccuuugucauccuucgccu 449
- miR-211
- miR-212
- uaacagucuccagucacggcc 450
- miR-212
- miR-213
- accaucgaccguugauuguacc 451
- miR-213
- miR-214
- acagcaggcacagacaggcag 452
- miR-214
- miR-215
- augaccuaugaauugacagac 453
- miR-215
- miR-216
- uaaucucagcuggcaacugug 454
- miR-216
- miR-217
- uacugcaucaggaacugauuggau 455
- miR-217
- miR-218
- uugugcuugaucuaaccaugu 456 miR-218-1; miR-218-2
- miR-219
- ugauuguccaaacgcaauucu 457 miR-219; miR-219-1; miR-219-2
- miR-220
- ccacaccguaucugacacuuu 458
- miR-220
- miR-221
- agcuacauugucugcuggguuuc 459
- miR-221
- miR-222
- agcuacaucuggcuacugggucuc 460
- miR-222
- miR-223
- ugucaguuugucaaauacccc 461
- miR-223
- miR-224
- caagucacuagugguuccguuua 462
- miR-224
- miR-296
- agggcccccccucaauccugu 463
- miR-296
- miR-299
- ugguuuaccgucccacauacau 464
- miR-299
- miR-301
- cagugcaauaguauugucaaagc 465
- miR-301
- miR-302a
- uaagugcuuccauguuuugguga 466
- miR-302a
- miR-302b*
- acuuuaacauggaagugcuuucu 467 miR-302b
- miR-302b
- uaagugcuuccauguuuuaguag 468
- miR-302b
- miR-302c*
- uuuaacauggggguaccugcug 469 miR-302c
- miR-302c
- uaagugcuuccauguuucagugg 470
- miR-302c
- miR-302d
- uaagugcuuccauguuugagugu 471
- miR-302d
- miR-320
- aaaagcuggguugagagggcgaa 472
- miR-320
- miR-321
- uaagccagggauuguggguuc 473
- miR-321
- miR-323
- gcacauuacacggucgaccucu 474
- miR-323
- miR-324-5p
- cgcauccccuagggcauuggugu 475 miR-324
- miR-324-3p
- ccacugccccaggugcugcugg 476 miR-324
- miR-325
- ccuaguagguguccaguaagu 477
- miR-325
- miR-326
- ccucugggcccuuccuccag 478
- miR-326
- miR-328
- cuggcccucucugcccuuccgu 479
- miR-328
- miR-330
- gcaaagcacacggccugcagaga 480
- miR-330
- miR-331
- gccccugggccuauccuagaa 481
- miR-331
- miR-335
- ucaagagcaauaacgaaaaaugu 482
- miR-335
- miR-337
- uccagcuccuauaugaugccuuu 483
- miR-337
- miR-338
- uccagcaucagugauuuuguuga 484
- miR-338
- miR-339
- ucccuguccuccaggagcuca 485
- miR-339
- miR-340
- uccgucucaguuacuuuauagcc 486
- miR-340
- miR-342
- ucucacacagaaaucgcacccguc 487
- miR-342
- miR-345
- ugcugacuccuaguccagggc 488
- miR-345
- miR-346
- ugucugcccgcaugccugccucu 489
- miR-346
- miR-367
- aauugcacuuuagcaaugguga 490
- miR-367
- miR-368
- acauagaggaaauuccacguuu 491
- miR-368
- miR-369
- aauaauacaugguugaucuuu 492
- miR-369
- miR-370
- gccugcugggguggaaccugg 493
- miR-370
- miR-371
- gugccgccaucuuuugagugu 494
- miR-371
- miR-372
- aaagugcugcgacauuugagcgu 495
- miR-372
- miR-373*
- acucaaaaugggggcgcuuucc 496 miR-373
- miR-373
- gaagugcuucgauuuuggggugu 497
- miR-373
- miR-374
- uuauaauacaaccugauaagug 498
- miR-374
La presente invención abarca métodos para diagnosticar si un sujeto tiene un cáncer de estómago, que comprenden medir el nivel de al menos miR-25 en una muestra de ensayo del sujeto y comparar el nivel de miR-25 en la muestra de ensayo con el nivel del correspondiente producto génico de miR en una muestra de control. Como se usa en la
5 presente memoria un “sujeto” puede ser cualquier mamífero que tenga, o se sospeche que tiene cáncer de estómago. En una realización preferida, el sujeto es un ser humano que tiene, o se sospecha que tiene, un cáncer de estómago.
También se desvelan en la presente memoria métodos en los que el al menos un producto génico de miR medido en
10 la muestra de ensayo se selecciona del grupo que consiste en miR-21, miR-17-5p, miR-191, miR-29b-2, miR-223, miR-128b, miR-199a-1, miR-24-1, miR-24-2, miR-146, miR-155, miR-181b-1, miR-20a, miR-107, miR-32, miR-92-2, miR-214, miR-30c, miR-25, miR-221, miR-106a y combinaciones de los mismos. También se desvelan en la presente memoria métodos en los que el producto génico de miR es miR-21, miR-191 o miR-17-5p. También se desvelan en la presente memoria métodos en los que el producto génico de miR no es miR-15a o miR-16-1.
15 También se desvelan en la presente memoria métodos en los que el producto génico de miR no es miR 159-1 o miR-192. También se desvelan en la presente memoria métodos en los que el producto génico de miR no es miR186, miR-101-1, miR-194, miR-215, miR-106b, miR-25, miR-93, miR-29b, miR-29a, miR-96, miR-182s, miR-182as, miR-183, miR-129-1, let-7a-1, let-7d, let-7f-1, miR-23b, miR-24-1, miR-27b, miR-32, miR-159-1, miR-192, miR-125b1, let-7a-2, miR-100, miR-196-2, miR-148b, miR-190, miR-21, miR-301, miR-142s, miR-142as, miR-105-1 o miR
20 175. También se desvelan en la presente memoria métodos en los que el producto génico de miR no es miR-21, miR-301, miR-142as, miR-142s, miR-194, miR-215 o miR-32. También se desvelan en la presente memoria métodos en los que el producto génico de miR no es miR-148, miR-10a, miR-196-1, miR-152, miR-196-2, miR-148b, miR-10b, miR-129-1, miR-153-2, miR-202, miR-139, let-7a, let-7f o let-7d. También se desvelan en la presente memoria métodos en los que el producto génico de miR no es miR-15a, miR-16-1, miR-182, miR-181, miR-30, miR-15a, miR
25 16-1, miR-15b, miR-16-2, miR-195, miR-34, miR-153, miR-21, miR-217, miR-205, miR-204, miR-211, miR-143, miR96, miR-103, miR-107, miR-129, miR-9, miR-137, miR-217, miR-186.
Los cánceres sólidos pueden ser cualquier cáncer que surja de órganos y tejidos sólidos. Dichos cánceres se asocian normalmente con la formación y/o presencia de masas tumorales y pueden ser carcinomas, sarcomas y 30 linfomas. Los ejemplos específicos de cánceres sólidos que pueden diagnosticarse por los métodos desvelados en la presente memoria incluyen, pero sin limitación, cáncer de colon, cáncer rectal, cáncer de estómago (gástrico),
- miR-23a (Nº 50)
- 0,022 -0,021
- miR-2.15 (Nº 213)
- 0,0204 -0,0194
- miR-7-2 (Nº 21)
- 0,0189 -0,018
- miR-138-2 (Nº 133)
- -0,0185 0,0176
- miR-24-1 (Nº 52)
- 0,0151 -0,0144
- miR-99b (Nº 89)
- 0,0098 -0,0093
- miR-33b (Nº 76)
- -0,0049 0,0046
- miR-24-2 (Nº 54)
- 0,0041 -0,0039
* -T=1, 28 miR seleccionados, error de clasificación equivocada después de validación cruzada de 0,19. Veintidós miR sobreexpresados en cáncer se indican por puntuaciones de cáncer positivas; 6 miR regulados negativamente se indican por puntuaciones de cáncer negativas.
Tabla 14. Los microARN compartidos por los distintivos de los 6 cánceres sólidos*.
- miR
- N Tipo de Tumor
- miR-21
- 6 Mama Colon Pulmón Páncreas Próstata Estómago
- miR-17-5p
- 5 Mama Colon Pulmón Páncreas Próstata
- miR-191
- 5 Colon Pulmón Páncreas Próstata Estómago
- miR-29b-2
- 4 Mama Colon Páncreas Próstata
- miR-223
- 4 Colon Páncreas Próstata Estómago
- miR-128b
- 3 Colon Pulmón Páncreas
- miR-199a-1
- 3 Pulmón Páncreas Próstata
- miR-24-1
- 3 Colon Páncreas Estómago
- miR-24-2
- 3 Colon Páncreas Estómago
- miR-146
- 3 Mama Páncreas Próstata
- miR-155
- 3 Mama Colon Pulmón
- miR-181b-1
- 3 Mama Páncreas Próstata
- miR-20a
- 3 Colon Páncreas Próstata
- miR-107
- 3 Colon Páncreas Estómago
- miR-32
- 3 Colon Páncreas Próstata
- miR-92-2
- 3 Páncreas Próstata Estómago
- miR-214
- 3 Páncreas Próstata Estómago
- miR-30c
- 3 Colon Páncreas Próstata
- miR-25
- 3 Páncreas Próstata Estómago
- miR-221
- 3 Colon Páncreas Estómago
- miR-106a
- 3 Colon Páncreas Próstata
- * -La lista incluye 21 microARN regulados positivamente habitualmente en 3 o más (N) tipos de cánceres sólidos (p valor = 2,5x10-3).
Para maximizar la concisión, se calcularon los niveles de expresión absolutos medios de los miR desregulados para 5 los 6 pares de cáncer/normal. Usando el nivel de expresión de los miR en el subconjunto exhaustivo, los diferentes tejidos se clasificaron correctamente independientemente de su estado de enfermedad (FIGURA 3).
La FIGURA 4 muestra la expresión diferencial de los microARN comunes entre los diferentes tejidos tumorales, en relación con los tejidos normales. El árbol presenta los diferentes tipos de cáncer según el factor de cambio en el
10 subconjunto de miARN. Los tejidos de próstata, colon, estómago y pancreático son más similares entre ellos, mientras que los tejidos de pulmón y de mama se representaron por un distintivo bastante diferente (FIGURA 4). Este árbol claramente muestra qué miARN están asociados con un histotipo de cáncer particular.
Sorprendentemente, miR-21, miR-191 y miR-17-5p están significativamente sobreexpresados en todos, o en 5 de 6,
15 de los tipos tumorales que se consideraron. Se indicó que miR-21 estaba sobreexpresado en glioblastoma y que tenía propiedades antiapoptóticas (Chan, J. A., et al., Cancer Res. 65: 6029-6033 (2005)). El cáncer de pulmón comparte una parte de su distintivo con el cáncer de mama y una parte con los otros tumores sólidos, incluyendo miR-17/20/92, los tres de los cuales son miembros del grupo de microARN que coopera activamente con c-Myc para acelerar la linfomagénesis (He, L., et al., Nature 435: 828-833 (2005)). La identificación de estos microARN como
20 sobreexpresados es una excelente confirmación del enfoque de los inventores. Un segundo grupo de miARN que está activado incluye miR-210 y miR-213, junto con miR-155, que ya se había indicado que estaba amplificado en linfomas de células grandes (Eis, P. S., et al., Proc. Natl. Acad Sci. USA 102: 3627-3632 (2005)), niños con linfoma de Burkitt (Metzler, M., et al., Genes Chromosomes Cancer 39: 167-169 (2004)) y diversos linfomas de linfocitos B
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