ES2490995T3 - Métodos basados en microARN y composiciones para el diagnóstico y el tratamiento de cánceres sólidos - Google Patents

Métodos basados en microARN y composiciones para el diagnóstico y el tratamiento de cánceres sólidos Download PDF

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ES2490995T3
ES2490995T3 ES12154304.5T ES12154304T ES2490995T3 ES 2490995 T3 ES2490995 T3 ES 2490995T3 ES 12154304 T ES12154304 T ES 12154304T ES 2490995 T3 ES2490995 T3 ES 2490995T3
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Carlo M. Croce
George A. Calin
Stefano Volinia
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Ohio State University Research Foundation
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Abstract

Un método para diagnosticar si un sujeto tiene un cáncer sólido, que comprende: medir el nivel de al menos un producto génico de miR-29b-2 en una muestra de ensayo del sujeto, en el que un aumento del nivel del producto génico de miR-29b-2 en la muestra de ensayo, en relación con el nivel del producto génico de miR-29b-2 en una muestra de control, es indicativa de que el sujeto tiene un cáncer sólido que es cáncer de colon o pancreático.

Description

imagen1
imagen2
imagen3
imagen4
imagen5
E12154304
07-08-2014
La FIGURA 8 representa transferencias de Northern que muestran regulación positiva de la expresión de miR103 y regulación negativa de la expresión de miR-155 (parte superior) en diferentes muestras de cáncer pancreático endocrino (WDET, tumores endocrinos pancreáticos bien diferenciados, WDEC, carcinomas endocrinos pancreáticos bien diferenciados y ACC, carcinomas de células de acinos pancreáticos) en relación
5 con muestras normales (serie K), así como regulación positiva de la expresión de miR-204 (parte inferior) en insulinomas (serie F) en relación con muestras normales (serie K) y muestras no secretoras/no actuantes (serie NF). Se realizó normalización con una sonda específica para ARN 5S.
Descripción detallada de la invención
10 La presente invención se basa, en parte, en la identificación de microARN particulares cuya expresión está alterada en células cancerosas asociadas con diferentes cánceres sólidos, tales como cáncer de colon, de estómago, pancreático, de pulmón, de mama y de próstata, en relación con células de control normales.
15 Como se usa en la presente memoria de forma intercambiable un “producto génico de miR”, “microARN”, “miR” o “miARN” se refiere al transcrito de ARN no procesado (por ejemplo, precursor) o procesado (por ejemplo, maduro) de un gen de miR. Ya que los productos génicos de miR no se traducen a proteína, la expresión “productos génicos de miR” no incluye proteínas. El transcrito génico de miR no procesado también se denomina un “precursor de miR”
o “miR prec” y típicamente comprende un transcrito de ARN de aproximadamente 70-100 nucleótidos de longitud. El
20 precursor de miR puede procesarse por digestión con una RNAsa (por ejemplo, Dicer, Argonaut o RNAsa III (por ejemplo RNAsa III de E. coli)) en una molécula de ARN de 19-25 nucleótidos activa. Esta molécula de ARN de 19-25 nucleótidos activa también se denomina el transcrito génico de miR “procesado” o miARN “maduro”.
La molécula de ARN de 19-25 nucleótidos activa puede obtenerse del precursor de miR mediante vías de
25 procesamiento naturales (por ejemplo, usando células intactas o lisados celulares) o mediante vías de procesamiento sintéticas (por ejemplo, usando enzimas de procesamiento aisladas, tales como Dicer, Argonaut o RNAsa III aislada). Se entiende que la molécula de ARN de 19-25 nucleótidos activa también puede producirse directamente por síntesis biológica o química, sin haberse procesado a partir del precursor de miR. Cuando se hace referencia a un microARN en la presente memoria por nombre, el nombre corresponde a las formas tanto
30 precursoras como maduras, a no ser que se indique de otro modo.
Las Tablas 1a y 1b representan las secuencias de nucleótidos de microARN humanos maduros y precursores particulares.
35 Tabla 1a-Secuencias precursoras de microARN humano
Nombre del Precursor
Secuencia (5’ a 3’) SEC ID Nº
let-7a-1
1
let-7a-2
2
let-7a-3
imagen6 3
let-7a-4
4
let-7b
5
let-7c
6
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07-08-2014 E12154304
let-7d
7
let-7d-v1
imagen7 8
let-7d-v2
9
let-7e
10
let-7f-1
11
let-7f-2-1
12
let-7f-2-2
13
let-7g
14
let-7i
imagen8 15
miR-1b-1-1
16
miR-1b-1-2
17
miR-1b-1-2
18
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miR-1b
19
miR-1d
imagen9 20
miR-7-1a
21
miR-7-16
22
miR-7-2
23
miR-7-3
imagen10 24
miR-9-1
25
miR-9-2
26
miR-9-3
27
miR-10a
imagen11 28
miR-10b
29
miR-15a-2
30
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miR-15a
31
miR-15b-1
imagen12 32
miR-15b-2
33
miR-16-1
34
miR-16-2
35
miR-16-13
imagen13 36
miR-17
37
miR-18
38
miR-18-13
39
miR-19a
imagen14 40
miR-19a-13
41
miR-19b-1
42
07-08-2014 E12154304
miR-19b-2
43
miR-19b-13
imagen15 44
miR-19b-X
45
miR-20 (miR20a)
46
miR-21
47
miR-21-17
imagen16 48
miR-22
49
miR-23a
50
miR-23b
51
miR-23-19
imagen17 52
miR-24-1
53
miR-24-2
54
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miR-24-19
55
miR-24-9
imagen18 56
miR-25
57
miR-26a
58
miR-26a-1
59
miR-26a-2
imagen19 60
miR-26b
61
miR-27a
62
miR-27b-1
63
miR-27b-2
imagen20 64
miR-27-19
65
miR-28
66
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miR-29a-2
67
miR-29a
imagen21 68
miR-29b-1
69
miR-29b-2
70
miR-29c
71
miR-30a
imagen22 72
miR-30b-1
73
miR-30b-2
74
miR-30c
75
miR-30d
imagen23 76
miR-30e
77
miR-31
78
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miR-32
79
miR-33b
imagen24 80
miR-33b-2
81
miR-33
82
miR-34-a
83
miR-34-b
imagen25 84
miR-34-c
85
miR-91-13
86
miR-92-1
87
miR-92-2
imagen26 88
miR-93-1 (miR-93-2)
89
miR-95-4
90
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miR-96-7
91
miR-97-6 (miR-30*)
imagen27 92
miR-98
93
miR-99b
94
miR-99a
95
miR-100-1/2
imagen28 96
miR-100-11
97
miR-101-1 /2
98
miR-101
99
miR-107-1
imagen29 100
miR-101-2
101
miR-101-9
102
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miR-102-1
103
miR-102-7.1 (miR-1027.2)
imagen30 104
miR-103-2
105
miR-103-1
106
miR-104-17
107
miR-105-1
imagen31 108
miR-105-2
109
miR-106-a
110
miR-106-b
111
miR-107
imagen32 112
miR-108-1pequeño
113
miR-108-2pequeño
114
07-08-2014 E12154304
miR-122a-1
115
miR-122a-2
imagen33 116
miR-123
117
miR-124a-1
118
miR-124a-2
119
miR-124a-3
imagen34 120
miR-124a
121
miR-124b
122
miR-125a-1
123
miR-125a-2
imagen35 124
miR-125b-1
125
miR-125b-2
126
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miR-126-1
127
miR-126-2
imagen36 128
miR-127-1
129
miR-127-2
130
miR-128a
131
miR-128b
imagen37 132
miR-128
133
miR-129-1
134
miR-129-2
135
miR-130a
imagen38 136
miR-131-1
137
miR-131-3
138
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miR-131
139
miR-132-1
imagen39 140
miR-132-2
141
miR-133a-1
142
miR-133a-2
143
miR-133
imagen40 144
miR-133b
145
miR-133bpequeño
146
miR-134-1
147
miR-134-2
imagen41 148
miR-135a-1
149
miR-135a-2 (miR-135-2)
150
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miR-135
151
miR-135b
imagen42 152
miR-136-1
153
miR-136-2
154
miR-137
155
miR-138-1
imagen43 156
miR-138-2
157
miR-138
158
miR-139
159
miR-140
imagen44 160
miR-140as
161
miR-140s
162
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miR-141-1
163
miR-141-2
imagen45 164
miR-142
165
miR-143-1
166
miR-143-2
167
miR-144-1
imagen46 168
miR-144-2
169
miR-145-1
170
miR-145-2
171
miR-146-1
imagen47 172
miR-146-2
173
miR-147
174
07-08-2014 E12154304
miR-148a (miR-148)
175
miR-148b
imagen48 176
miR-148bpequeño
177
miR-149-1
178
miR-149-2
179
miR-150-1
imagen49 180
miR-150-2
181
miR-151
182
miR-151-2
183
miR-152-1
imagen50 184
miR-152-2
185
miR-153-1-1
186
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miR-153-1-2
187
miR-153-2-1
imagen51 188
miR-153-2-2
189
miR-154-1
190
miR-154-2
191
miR-155
imagen52 192
miR-156 = miR-157 = solapamiento con miR-141
193
miR-158pequeño = miR-192
194
miR-159-1pequeño
195
miR-161pequeño
imagen53 196
miR-163-1bpequeño
197
miR-163-3pequeño
198
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miR-162
199
miR-175pequeño = miR-224
imagen54 200
miR-177pequeño
201
miR-180pequeño
202
miR-181a
203
miR-187b-1
imagen55 204
miR-181b-2
205
miR-181c
206
miR-182-as
207
miR-182
imagen56 208
miR-183
209
miR-184-1
210
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miR-184-2
211
miR-185-1
imagen57 212
miR-185-2
213
miR-186-1
214
miR-186-2
215
miR-187
imagen58 216
miR-188-1
217
miR-188-2
218
miR-189-1
219
miR-189-2
imagen59 220
miR-190-1
221
miR-190-2
222
07-08-2014 E12154304
miR-191-1
223
miR-191-2
imagen60 224
miR-192-2/3
225
miR-192
226
miR-193-1
227
miR-193-2
imagen61 228
miR-194-1
229
miR-194-2
230
miR-195-1
231
miR-195-2
imagen62 232
miR-196-1
233
miR-196a-1
234
07-08-2014 E12154304
miR-196a-2 (miR-196-2)
235
miR-196
imagen63 236
miR-196b
237
miR-197
238
miR-197-2
239
miR-198
imagen64 240
miR-199a-1
241
miR-199a-2
242
miR-199b
243
miR-199s
imagen65 244
miR-200a
245
miR-200b
246
07-08-2014 E12154304
miR-200c
247
miR-202
imagen66 248
miR-203
249
miR-204
250
miR-205
251
miR-206-7
imagen67 252
miR-206-2
253
miR-208
254
miR-210
255
miR-211
imagen68 256
miR-212
257
miR-213-2
258
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miR-213
259
miR-214
imagen69 260
miR-215
261
miR-216
262
miR-217
263
miR-218-1
imagen70 264
miR-218-2
265
miR-219
266
miR-219-1
267
miR-219-2
imagen71 268
miR-220
269
miR-221
270
07-08-2014 E12154304
miR-222
271
miR-223
imagen72 272
miR-224
273
miR-294-1 (chr16)
274
miR-296
275
miR-299
imagen73 276
miR-301
277
miR-302a
278
miR-302b
279
miR-302c
imagen74 280
miR-302d
281
miR-320
282
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miR-321
283
miR-323
imagen75 284
miR-324
285
miR-325
286
miR-326
287
miR-328
imagen76 288
miR-330
289
miR-331
290
miR-335
291
miR-337
imagen77 292
miR-338
293
miR-339
294
07-08-2014 E12154304
miR-340
295
miR-342
imagen78 296
miR-345
297
miR-346
298
miR-367
299
miR-368
imagen79 300
miR-369
301
miR-370
302
miR-371
303
miR-372
imagen80 304
miR-373
305
miR-374
306
07-08-2014
miR-hes1
307
miR-hes2
imagen81 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-vl
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 18 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)
E12154304
07-08-2014 E12154304
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
07-08-2014 E12154304
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-12-1a-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
07-08-2014 E12154304
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
uagguaguuuccuguuguugg 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
07-08-2014 E12154304
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
07-08-2014
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 sólido, que comprenden medir el nivel de al menos un primer producto génico de miR-29b-2 en una muestra de ensayo del sujeto y comparar el nivel del producto génico de miR en la muestra de ensayo con el nivel del producto génico de miR correspondiente
5 en una muestra de control. Como se usa en la presente memoria un “sujeto” puede ser cualquier mamífero que tenga, o se sospeche que tiene, un cáncer sólido. En una realización preferida, el sujeto es un ser humano que tiene, o se sospecha que tiene, un cáncer sólido.
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 típicamente 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), cáncer pancreático, cáncer de mama, cáncer de pulmón, cáncer de próstata, cáncer bronquial, cáncer testicular, cáncer ovárico, cáncer uterino, cáncer peniano, melanoma y otros cánceres de la piel, cáncer de hígado, cáncer esofágico, cánceres de la cavidad oral y faringe (por ejemplo, cáncer de lengua, cáncer de boca), cánceres del 35 sistema digestivo (por ejemplo, cáncer intestinal, cáncer de la vesícula biliar), cánceres de huesos y articulaciones, cánceres del sistema endocrino (por ejemplo, cáncer tiroideo), cáncer de cerebro, cáncer de ojo, cánceres del sistema urinario (por ejemplo, cáncer de riñón, cáncer de la vejiga urinaria), enfermedad de Hodgkin y linfoma no de Hodgkin. Los cánceres sólidos pueden no ser uno o más de cáncer de mama, cáncer de pulmón, cáncer de próstata,
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ES12154304.5T 2006-01-05 2007-01-03 Métodos basados en microARN y composiciones para el diagnóstico y el tratamiento de cánceres sólidos Active ES2490995T3 (es)

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