exoRNA määrityksen sovellus

KEUHKO, PULM.
EXoRNA
Keuhkosyövistä  suurin osa (85%) on  tyyppiä -ei-pienisoluinen keuhkokarsinooma. NSCLC, Non Small Cell Lung Cancer,  icke småcellig lungcancer .
Näissä  kehkosyövissä  on alatyyppi, jossa metastaasit  ovat rintaontelon sisäisiä, intratorakaalisia (M0/M1a)  ja sille  on tyypillistä että kiertävän soluvapaan  DNA:n määrät ovat vähäiset (cellfree DNA, cf-DNA), mikä on suuri  diagnostinen haaste.
Tutkijaryhmä on selvittänyt voitaisiinko kombinoida  exosomaalisen RNA:n (exoRNA)  ja cfDNA:n määritykset  tarkoituksena havaita EGFR-mutaatiot. Diagnostinen herkkyys parani erityisesti  mainitussa syöpäalatyypissä.


Improved EGFR mutation detection using combined exosomal RNA and circulating tumor DNA in NSCLC patient plasma.
Krug AK, Enderle D, Karlovich C, Priewasser T, Bentink S, Spiel A, Brinkmann K, Emenegger J, Grimm DG,
 Castellanos-Rizaldos E, Goldman JW, Sequist LV, Soria JC, Camidge DR, Gadgeel SM, Wakelee HA, Raponi M, Noerholm M, Skog J.
Ann Oncol. 2017 Dec 5. doi: 10.1093/annonc/mdx765. [Epub ahead of print]
Background:

A major limitation of circulating tumor DNA (ctDNA) for somatic mutation detection has been the low level  of ctDNA found in a subset of cancer patients.
We investigated whether using a combined isolation of exosomal RNA (exoRNA) and cell-free DNA (cfDNA) could improve blood-based liquid biopsy for EGFR mutation detection in NSCLC patients.
Patients and methods: Matched pretreatment tumor and plasma were collected from 84 patients enrolled in TIGER-X (NCT01526928),
 a Ph1/2 study of rociletinib in mutant EGFR NSCLC patients. The combined isolated exoRNA and cfDNA (exoNA)  was analyzed for mutations using a targeted NGS panel (EXO1000), and compared to existing data from the same samples using analysis of ctDNA by BEAMing.
Results:
For exoNA, the sensitivity was 98% for detection of activating EGFR mutations and 90% for EGFR T790M. The corresponding sensitivities for ctDNA by BEAMing were 82% for activating mutations and 84% for T790M.
In a subgroup of patients with intrathoracic metastatic disease (M0/M1a; n = 21), the sensitivity increased from 26% to 74% for activating mutations (p = 0.003) and from 19% to 31% for T790M (p = 0.5) when using exoNA for detection.
Conclusions:
Combining exoRNA and ctDNA increased the sensitivity for EGFR mutation detection in plasma,  with the largest improvement seen in the subgroup of M0/M1a disease patients known to have  low levels of ctDNA which poses challenges for ctDNA-only based mutation detection.
PMID:
    29216356

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