Descripción general
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Los síndromes de cáncer hereditario se encuentran en todas las especialidades médicas. Aunque representan alrededor del 5% de todas las neoplasias malignas, es de especial importancia identificar a estos pacientes porque, a diferencia de los pacientes con cánceres esporádicos, requieren cuidados especiales a largo plazo ya que su predisposición puede hacer que desarrollen ciertos tumores a una edad relativamente temprana. edad. Estos cánceres pueden surgir en los pulmones, riñones, hígado, páncreas, piel, ojos, corazón. La mayoría de los cánceres hereditarios están asociados con una «mutación de la línea germinal» que estará presente en todas las células del cuerpo humano. La identificación de pacientes con riesgo de susceptibilidad hereditaria al cáncer depende de la capacidad de caracterizar genes y alteraciones asociadas con un mayor riesgo de cáncer, así como recopilación de antecedentes personales y familiares detallados que ayuden a identificar la modalidad de herencia, así como a otros familiares en riesgo de padecer esta susceptibilidad. La mayoría de los síndromes de cáncer hereditario siguen una herencia autosómica dominante y la penetrancia es alta.
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El Panel integral de precisión del cáncer heredado de Igenomix proporciona un análisis completo de los síndromes de cáncer hereditario más comunes utilizando la secuenciación de próxima generación (NGS) para comprender completamente el espectro de genes de predisposición al cáncer relevantes.
Indicaciones
El panel de precisión de cáncer heredado integral está indicado como prueba de detección y diagnóstico en aquellos casos en los que existan:
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Varios parientes del mismo lado de la familia con el mismo cáncer o formas relacionadas
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Cáncer a temprana edad
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Presentación temprana de un tipo de cáncer agresivo
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Múltiples cánceres primarios en un individuo
Utilidad clínica
La utilidad clínica de este panel es:
-
Diagnóstico genético precoz y preciso que permite el manejo clínico más adecuado de un paciente con antecedentes personales o familiares sugestivos de un síndrome oncológico hereditario.
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Intensificación de la vigilancia y participación en programas de detección temprana para la prevención del cáncer.
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Inicio precoz del tratamiento o intervención quirúrgica.
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Evaluación de riesgo de familiares asintomáticos según modalidad hereditaria y asesoramiento genético de familiares.
Genes y enfermedades
Lista de genes incluidos en el Panel integral de precisión del cáncer heredado.
Los genes más relevantes se han clasificado según:
|
Alto riesgo |
Bien estudiado |
|
|
Riesgo mayor de 4 veces de desarrollar uno o más cánceres |
|
|
Puede causar un riesgo moderado de otros cánceres.
|
|
|
Directrices u opinión de expertos para la detección y la prevención del cáncer |
|
Riesgo moderado |
Bien estudiado |
|
|
Riesgo de 2 a 4 veces mayor de desarrollar uno o más cánceres
|
|
|
Puede aumentar el riesgo de otros cánceres |
|
|
Directrices limitadas para la detección y la prevención |
|
Investigar |
No tan bien estudiado |
|
|
Los riesgos precisos de por vida y el espectro tumoral aún no se han determinado |
|
|
Las pautas para la detección y la prevención son limitadas o no están disponibles |
Ver todos los genes y enfermedades
|
GENE |
RISK |
INHERITANCE* |
% GENE COVERAGE (20X) |
HGMD** |
|
AIP |
AD,AR |
100% |
103 of 106 |
|
|
AKT1 |
Moderate |
AD |
100% |
6 of 6 |
|
ALK |
99.84% |
16 of 16 |
||
|
ANKRD26 |
AD |
98.76% |
3 of 23 |
|
|
APC |
High |
AD |
98.92% |
1846 of 1882 |
|
AR |
AD,X,XR,G |
97.96% |
NA of NA |
|
|
ATM |
Moderate |
AD,AR |
99.93% |
1608 of 1632 |
|
AXIN2 |
AD |
99.86% |
32 of 33 |
|
|
BAP1 |
AD |
100% |
194 of 195 |
|
|
BARD1 |
Moderate |
AD |
99.86% |
195 of 195 |
|
BLM |
AR |
97.19% |
133 of 141 |
|
|
BMPR1A |
High |
AD |
100% |
124 of 127 |
|
BRAF |
AD |
100% |
80 of 80 |
|
|
BRCA1 |
High |
AD,AR,MU |
98.97% |
2783 of 2894 |
|
BRCA2 |
High |
AD,AR,MU |
98.51% |
3343 of 3451 |
|
BRE |
98.20% |
NA of NA |
||
|
BRIP1 |
Moderate |
AD,AR |
94.97% |
235 of 237 |
|
BUB1B |
AD,AR |
99.84% |
30 of 31 |
|
|
CBL |
AD |
100% |
46 of 47 |
|
|
CD70 |
AR |
99.89% |
4 of 4 |
|
|
CD82 |
100% |
NA of NA |
||
|
CDC73 |
AD |
100% |
95 of 95 |
|
|
CDH1 |
High |
AD |
100% |
361 of 363 |
|
CDK4 |
AD |
100% |
22 of 22 |
|
|
CDKN1B |
AD |
99.99% |
19 of 20 |
|
|
CDKN1C |
AD |
73.58% |
55 of 76 |
|
|
CDKN2A |
High |
AD |
94.99% |
257 of 262 |
|
CEBPA |
AD |
67.47% |
14 of 17 |
|
|
CEP57 |
AR |
99.64% |
6 of 6 |
|
|
CHEK2 |
Moderate |
AD |
99.47% |
307 of 310 |
|
CYLD |
AD |
99% |
114 of 116 |
|
|
DDB2 |
AR |
100% |
17 of 17 |
|
|
DDX41 |
AD |
99.99% |
56 of 56 |
|
|
DICER1 |
AD |
99.98% |
178 of 180 |
|
|
DIS3L2 |
AR |
99.99% |
12 of 13 |
|
|
DKC1 |
X,XR,G |
100% |
NA of NA |
|
|
EFL1 |
AR |
99.94% |
NA of NA |
|
|
EGFR |
AD,AR |
100% |
27 of 27 |
|
|
ELAC2 |
AR |
100% |
32 of 32 |
|
|
ELANE |
AD |
100% |
227 of 227 |
|
|
ENG |
AD |
100% |
467 of 471 |
|
|
EPCAM |
High |
AR |
99.94% |
52 of 70 |
|
ERCC1 |
AR |
93.12% |
6 of 6 |
|
|
ERCC2 |
AR |
100% |
102 of 102 |
|
|
ERCC3 |
AR |
99.98% |
24 of 24 |
|
|
ERCC4 |
AR |
99.68% |
69 of 72 |
|
|
ERCC5 |
AR |
99.94% |
58 of 58 |
|
|
ETV6 |
AD |
100% |
41 of 41 |
|
|
EXO1 |
99.86% |
17 of 17 |
||
|
EXT1 |
AD,AR |
99.97% |
518 of 525 |
|
|
EXT2 |
AD,AR |
100% |
251 of 254 |
|
|
EZH2 |
AD |
99.82% |
40 of 41 |
|
|
FAM111B |
AD |
97.88% |
10 of 10 |
|
|
FAM175A |
94.81% |
NA of NA |
||
|
FANCA |
AR |
95.17% |
497 of 502 |
|
|
FANCB |
X,XR,G |
95.53% |
NA of NA |
|
|
FANCC |
AR |
100% |
75 of 75 |
|
|
FANCD2 |
AR |
100% |
62 of 63 |
|
|
FANCE |
AR |
97% |
17 of 18 |
|
|
FANCF |
AR |
99.31% |
17 of 18 |
|
|
FANCG |
100% |
94 of 94 |
||
|
FANCI |
AR |
100% |
53 of 54 |
|
|
FANCL |
AR |
100% |
25 of 26 |
|
|
FANCM |
AR |
99.73% |
59 of 61 |
|
|
FH |
High |
AD,AR |
100% |
229 of 232 |
|
FLCN |
High |
AD |
100% |
200 of 205 |
|
GALNT12 |
88.97% |
14 of 15 |
||
|
GATA2 |
AD |
100% |
137 of 142 |
|
|
GEN1 |
99.71% |
6 of 6 |
||
|
GPC3 |
AD,X,XR,G |
99.84% |
NA of NA |
|
|
GREM1 |
99.89% |
5 of 5 |
||
|
HNF1A |
AD |
100% |
529 of 538 |
|
|
HOXB13 |
100% |
5 of 5 |
||
|
HRAS |
AD |
100% |
34 of 34 |
|
|
IKZF1 |
AD |
99.98% |
43 of 43 |
|
|
KIF1B |
AD |
99.89% |
17 of 17 |
|
|
KIT |
AD |
100% |
112 of 112 |
|
|
KITLG |
AD |
99.93% |
10 of 10 |
|
|
KRAS |
AD |
100% |
38 of 38 |
|
|
LZTR1 |
AD |
99.99% |
136 of 136 |
|
|
MAP2K1 |
AD |
100% |
31 of 31 |
|
|
MAP2K2 |
AD |
100% |
37 of 37 |
|
|
MAX |
AD |
99.32% |
33 of 33 |
|
|
MEN1 |
AD |
99.90% |
871 of 876 |
|
|
MET |
AD,AR |
99.80% |
41 of 41 |
|
|
MITF |
AD,AR |
100% |
72 of 72 |
|
|
MLH1 |
High |
AD,AR |
99.94% |
1079 of 1118 |
|
MLH3 |
AD |
99.98% |
32 of 32 |
|
|
MRE11 |
AR |
99.95% |
NA of NA |
|
|
MSH2 |
High |
AD,AR |
99.99% |
1032 of 1057 |
|
MSH3 |
AD,AR |
99.42% |
23 of 24 |
|
|
MSH6 |
High |
AD,AR |
99.28% |
613 of 641 |
|
MSR1 |
100% |
16 of 16 |
||
|
MUTYH |
High |
AR |
100% |
183 of 183 |
|
MXI1 |
AD |
94.55% |
NA of NA |
|
|
NBN |
AR,MU,P |
100% |
200 of 200 |
|
|
NF1 |
High |
AD |
97.97% |
3082 of 3166 |
|
NF2 |
AD |
100% |
359 of 362 |
|
|
NRAS |
AD |
100% |
15 of 15 |
|
|
NSD1 |
AD |
99.80% |
451 of 459 |
|
|
NSUN2 |
AR |
99.99% |
8 of 8 |
|
|
NTHL1 |
AR |
100% |
13 of 13 |
|
|
PALB2 |
High |
AD,AR |
98.78% |
601 of 617 |
|
PAX5 |
100% |
8 of 8 |
||
|
PDGFRA |
AD |
100% |
24 of 24 |
|
|
PHB |
AD |
100% |
1 of 1 |
|
|
PHOX2B |
AD |
90.74% |
58 of 71 |
|
|
PIK3CA |
AD |
99.58% |
54 of 58 |
|
|
PMS1 |
AD |
99.92% |
32 of 33 |
|
|
PMS2 |
High |
AD,AR |
97.17% |
264 of 285 |
|
POLD1 |
AD |
100% |
40 of 41 |
|
|
POLE |
AD,AR |
100% |
100 of 100 |
|
|
POLH |
AR |
99.49% |
73 of 76 |
|
|
POT1 |
AD |
99.76% |
42 of 47 |
|
|
PPM1D |
AD |
97.82% |
76 of 79 |
|
|
PRF1 |
AR |
99.99% |
196 of 196 |
|
|
PRKAR1A |
AD |
95.93% |
165 of 171 |
|
|
PTCH1 |
AD |
98.89% |
498 of 502 |
|
|
PTEN |
High |
AD |
99.97% |
609 of 629 |
|
PTPN11 |
AD |
100% |
150 of 151 |
|
|
RAD50 |
AR |
99.94% |
117 of 120 |
|
|
RAD51C |
Moderate |
AR |
100% |
130 of 130 |
|
RAD51D |
Moderate |
100% |
97 of 97 |
|
|
RAD54L |
AD |
100% |
4 of 4 |
|
|
RAF1 |
AD |
100% |
64 of 64 |
|
|
RASA2 |
99.82% |
5 of 5 |
||
|
RB1 |
AD |
99.41% |
941 of 995 |
|
|
RB1CC1 |
AD |
99.30% |
1 of 1 |
|
|
RECQL |
99.71% |
32 of 34 |
||
|
RECQL4 |
AR |
96.72% |
134 of 135 |
|
|
REST |
AD |
99.83% |
15 of 16 |
|
|
RET |
AD |
100% |
453 of 454 |
|
|
RHBDF2 |
AD |
99.27% |
5 of 5 |
|
|
RINT1 |
AR |
99.96% |
16 of 16 |
|
|
RIT1 |
AD |
99.85% |
27 of 27 |
|
|
RNASEL |
AD |
99.83% |
7 of 7 |
|
|
RPS20 |
99.97% |
1 of 1 |
||
|
RRAS |
95.86% |
3 of 3 |
||
|
RUNX1 |
AD |
99.83% |
90 of 90 |
|
|
SAMD9 |
AD,AR |
99.72% |
45 of 46 |
|
|
SAMD9L |
AD |
99.81% |
39 of 39 |
|
|
SBDS |
AR |
100% |
77 of 79 |
|
|
SDHA |
AD,AR,MI |
99.98% |
103 of 103 |
|
|
SDHAF2 |
AD |
96.78% |
8 of 8 |
|
|
SDHB |
High |
AD |
100% |
261 of 264 |
|
SDHC |
AD |
99.95% |
62 of 63 |
|
|
SDHD |
AD,AR |
99.98% |
164 of 166 |
|
|
SHOC2 |
AD |
99.98% |
8 of 8 |
|
|
SLC22A18 |
AD,AR |
99.98% |
1 of 1 |
|
|
SLX4 |
AR |
99.92% |
76 of 76 |
|
|
SMAD4 |
High |
AD |
99.56% |
136 of 136 |
|
SMARCA4 |
AD |
100% |
68 of 69 |
|
|
SMARCB1 |
AD |
100% |
97 of 99 |
|
|
SOS1 |
AD |
100% |
103 of 104 |
|
|
SOS2 |
AD |
99.48% |
6 of 7 |
|
|
SPRED1 |
AD |
100% |
84 of 84 |
|
|
SRP72 |
AD |
99.95% |
3 of 3 |
|
|
STK11 |
High |
AD |
81.99% |
456 of 470 |
|
SUFU |
AD,AR |
99.99% |
43 of 43 |
|
|
TERC |
AD |
na |
na |
|
|
TERT |
AD,AR |
99.09% |
194 of 197 |
|
|
TGFBR2 |
AD |
99.90% |
165 of 166 |
|
|
TINF2 |
AD |
99.94% |
47 of 47 |
|
|
TMEM127 |
||||
|
TP53 |
High |
AD,MU,P |
98.92% |
557 of 563 |
|
TSC1 |
High |
AD |
99.86% |
390 of 406 |
|
TSC2 |
High |
AD |
100% |
1157 of 1159 |
|
VHL |
High |
AD,AR |
100% |
511 of 544 |
|
WRN |
AR |
99.97% |
107 of 109 |
|
|
WT1 |
AD |
98.92% |
178 of 185 |
|
|
XPA |
AR |
99.91% |
49 of 49 |
|
|
XPC |
AR |
99.83% |
86 of 87 |
|
|
XRCC2 |
AR |
98.39% |
28 of 28 |
|
|
XRCC3 |
AD |
100% |
11 of 11 |
|
* Herencia: AD: Autosómico Dominante; AR: autosómico recesivo; X: ligado a X; XLR: recesivo vinculado a X; Mi: mitocondrial; Mu: multifactorial; G: herencia gonosomal; D: herencia digénica
** HGMD: número de mutaciones clínicamente relevantes según HGMD
Referencias
LaDuca et al. A clinical guide to hereditary cancer panel testing: evaluation of gene-specific cancer associations and sensitivity of genetic testing criteria in a cohort of 165,000 high-risk patients. Genet Med 22, 407–415 (2020). https://doi.org/10.1038/s41436-019-0633-8
Breast Cancer Association Consortium, Dorling L, et al. Breast Cancer Risk Genes – Association Analysis in More than 113,000 Women. N Engl J Med. 2021 Jan 20. doi: 10.1056/NEJMoa1913948. Epub ahead of print. PMID: 33471991.
Rahner, N., & Steinke, V. (2008). Hereditary cancer syndromes. Deutsches Arzteblatt international, 105(41), 706–714. https://doi.org/10.3238/arztebl.2008.0706
Syngal, S., Brand, R. E., Church, J. M., Giardiello, F. M., Hampel, H. L., Burt, R. W., & American College of Gastroenterology (2015). ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. The American journal of gastroenterology, 110(2), 223–263. https://doi.org/10.1038/ajg.2014.435
Li et al. (2020). Points to consider for reporting of germline variation in patients undergoing tumor testing: a statement of the American College of Medical Genetics and Genomics (ACMG). Genetics In Medicine, 22(7), 1142-1148. doi: 10.1038/s41436-020-0783-8
Garber, J. E., & Offit, K. (2005). Hereditary cancer predisposition syndromes. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 23(2), 276–292. https://doi.org/10.1200/JCO.2005.10.042
National Comprehensive Cancer Network. (2021). https://www.nccn.org/professionals/physician_gls/default.aspx#detection
