Omic Approach in Non-smoker Female with Lung Squamous Cell Carcinoma Pinpoints to Germline Susceptibility and Personalized Medicine / Journal of the Korean Cancer Association, 대한암학회지
Cancer Research and Treatment
;
: 356-365, 2018.
Article
Dans Anglais
| WPRIM
| ID: wpr-713897
ABSTRACT
PURPOSE:
Lung cancer is strongly associated to tobacco smoking. However, global statistics estimate that in females the proportion of lung cancer cases that is unrelated to tobacco smoking reaches fifty percent, making questionable the etiology of the disease. MATERIALS ANDMETHODS:
A never-smoker female with primary EGFR/KRAS/ALK-negative squamous cell carcinoma of the lung and their normal sibswere subjected to a novel integrative “omic” approach using a pedigree-based model for discovering genetic factors leading to cancer in the absence of well-known environmental trigger. A first-stepwhole-exome sequencing on tumor and normal tissue did not identify mutations in known driver genes. Building on the idea of a germline oligogenic origin of lung cancer, we performed whole-exome sequencing of DNA from patients' peripheral blood and their unaffected sibs. Finally, RNA-sequencing analysis in tumoral and matched non-tumoral tissues was carried out in order to investigate the clonal profile and the pathogenic role of the identified variants.RESULTS:
Filtering for rare variants with Combined Annotation Dependent Depletion (CADD) > 25 and potentially damaging effect, we identified rare/private germline deleterious variants in 11 cancer-associated genes, none ofwhich, except one, sharedwith the healthy sib, pinpointing to a “private” oligogenic germline signature. Noteworthy, among these, two mutated genes, namely ACACA and DEPTOR, turned to be potential targets for therapy because related to known drivers, such as BRCA1 and EGFR.CONCLUSION:
In the era of precision medicine, this report emphasizes the importance of an “omic” approach to uncover oligogenic germline signature underlying cancer development and to identify suitable therapeutic targets as well.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
ADN
/
Carcinome épidermoïde
/
Fumer
/
Hérédité multifactorielle
/
Prédisposition aux maladies
/
Cellules épithéliales
/
Médecine de précision
/
Séquençage nucléotidique à haut débit
/
Exome
/
Poumon
Type d'étude:
Étude pronostique
Limites du sujet:
Femelle
/
Humains
langue:
Anglais
Texte intégral:
Cancer Research and Treatment
Année:
2018
Type:
Article
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