nemoci-sympt/ONKOLOGIE/nadory-prostaty/diagnostika/vzorky-na-genetiku-meta-ca

Circulating cell-free DNA (cfDNA)

• May be another avenue for identifying DNA repair mutations
• Relatively non-invasive [4]
• Targeted and whole-exome sequencing of serial circulating cell-free DNA (cfDNA) samples
• Decreases in cfDNA concentration independently associated with outcome in multivariable analyses
• All tumor tissue somatic DNA repair mutations were detectable in cfDNA
• Allele frequency of somatic mutations decreased selectively in teraphy responding patients
• At disease progression, following response to olaparib
• Multiple subclonal aberrations reverting germline and somatic DNA repair mutations (BRCA2, PALB2) back in frame emerged as mechanisms of resistance [6]

Biopsie kosti

• Bone biopsies obtain tumor only 69% of the time
• Genetic sequencing on bone biopsies requires removal of the bone matrix
• Process that can damage tumor cell integrity
• Sequencing success rate of 67% (compared with 80% for non-bone sites) [4]

Biopsie prostaty

• Only 4% of patients had 5 or more new mutations in the metastatic specimen
• In 26% of the cases, mutational profiles were identical
• DNA repair genes, all aberrations in primary tumors were present in mCRPC biopsies
• In 6.8% of cases, a DNA repair aberration was found only in the mCRPC biopsy
• Mateo et al, 49 paired biopsies were sequenced
• All mutations in BRCA2 and ATM were shared between the primary and metastatic biopsies [4]

Genetické testy

• According to the NCCN guidelines for genetic testing in 2018, testing should be performed in all metastatic PC patients [5]