Tumor analysis of MMR genes in Lynch-like syndrome: Challenges associated with results interpretation.
Cancer Med
; 13(7): e7041, 2024 Apr.
Article
in En
| MEDLINE
| ID: mdl-38558366
ABSTRACT
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 ANDDISCUSSION:
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Neoplastic Syndromes, Hereditary
/
Brain Neoplasms
/
Colorectal Neoplasms
/
Colorectal Neoplasms, Hereditary Nonpolyposis
Limits:
Humans
Language:
En
Journal:
Cancer Med
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: