Tumor analysis of MMR genes in Lynch-like syndrome: Challenges associated with results interpretation
Por:
Rofes, P, Dueñas, N, del Valle, J, Navarro, M, Balmaña, J, Ramón y Cajal, T, Tuset, N, Castillo, C, González, S, Brunet, J, Capellá, G, Lázaro, C, Pineda, M
Publicada:
1 abr 2024
Resumen:
Background: Up to 70% of suspected Lynch syndrome patients harboring MMR deficient tumors lack identifiable germline pathogenic variants in MMR genes, being referred to as Lynch-like syndrome (LLS). Previous studies have reported biallelic somatic MMR inactivation in a variable range of LLS-associated tumors. Moreover, translating tumor testing results into patient management remains controversial. Our aim is to assess the challenges associated with the implementation of tumoral MMR gene testing in routine workflows. Methods: Here, we present the clinical characterization of 229 LLS patients. MMR gene testing was performed in 39 available tumors, and results were analyzed using two variant allele frequency (VAF) thresholds (>= 5% and >= 10%). Results and Discussion: More biallelic somatic events were identified at VAF >= 5% than >= 10% (35.9% vs. 25.6%), although the rate of nonconcordant results regarding immunohistochemical pattern increased (30.8% vs. 20.5%). Interpretation difficulties question the current utility of the identification of MMR somatic hits in the diagnostic algorithm of suspected LS cases.
Filiaciones:
Rofes, P:
Catalan Inst Oncol, Inst Invest Biomed Bellvitge IDIBELL, Hereditary Canc Program, Mol Mech & Expt Therapy Oncol Program, Lhospitalet De Llobregat, Spain
Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain
Dueñas, N:
Catalan Inst Oncol, Inst Invest Biomed Bellvitge IDIBELL, Hereditary Canc Program, Mol Mech & Expt Therapy Oncol Program, Lhospitalet De Llobregat, Spain
Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain
del Valle, J:
Catalan Inst Oncol, Inst Invest Biomed Bellvitge IDIBELL, Hereditary Canc Program, Mol Mech & Expt Therapy Oncol Program, Lhospitalet De Llobregat, Spain
Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain
Navarro, M:
Catalan Inst Oncol, Inst Invest Biomed Bellvitge IDIBELL, Hereditary Canc Program, Mol Mech & Expt Therapy Oncol Program, Lhospitalet De Llobregat, Spain
Balmaña, J:
Vall dHebron Hosp, Vall dHebron Inst Oncol VHIO, Hereditary Canc Genet Grp, Barcelona, Spain
Ramón y Cajal, T:
Hosp Santa Creu & Sant Pau, Med Oncol Dept, Barcelona, Spain
Tuset, N:
Arnau de Vilanova Univ Hosp, Med Oncol Dept, Lleida, Spain
Castillo, C:
Catalan Inst Oncol, Inst Invest Biomed Bellvitge IDIBELL, Hereditary Canc Program, Mol Mech & Expt Therapy Oncol Program, Lhospitalet De Llobregat, Spain
González, S:
Catalan Inst Oncol, Inst Invest Biomed Bellvitge IDIBELL, Hereditary Canc Program, Mol Mech & Expt Therapy Oncol Program, Lhospitalet De Llobregat, Spain
Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain
Brunet, J:
Catalan Inst Oncol, Inst Invest Biomed Bellvitge IDIBELL, Hereditary Canc Program, Mol Mech & Expt Therapy Oncol Program, Lhospitalet De Llobregat, Spain
Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain
Catalan Inst Oncol IDIBGI, Hereditary Canc Program, Girona, Spain
Capellá, G:
Catalan Inst Oncol, Inst Invest Biomed Bellvitge IDIBELL, Hereditary Canc Program, Mol Mech & Expt Therapy Oncol Program, Lhospitalet De Llobregat, Spain
Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain
Lázaro, C:
Catalan Inst Oncol, Inst Invest Biomed Bellvitge IDIBELL, Hereditary Canc Program, Mol Mech & Expt Therapy Oncol Program, Lhospitalet De Llobregat, Spain
Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain
Pineda, M:
Catalan Inst Oncol, Inst Invest Biomed Bellvitge IDIBELL, Hereditary Canc Program, Mol Mech & Expt Therapy Oncol Program, Lhospitalet De Llobregat, Spain
Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain
Catalan Inst Oncol, Hereditary Canc Program, IDIBELL, Av Gran Via 199-203, Lhospitalet De Llobregat 08908, Spain
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