Integrated Somatic and Germline Whole-Exome Sequencing Analysis in Women with Lung Cancer after a Previous Breast Cancer.
breast cancer
exome sequencing
genetic predisposition
lung cancer
multiple cancer susceptibility
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
28 Mar 2019
28 Mar 2019
Historique:
received:
08
02
2019
revised:
12
03
2019
accepted:
25
03
2019
entrez:
31
3
2019
pubmed:
31
3
2019
medline:
31
3
2019
Statut:
epublish
Résumé
Women treated for breast cancer (BC) are at risk of developing secondary tumors, such as lung cancer (LC). Since rare germline variants have been linked to multiple cancer development, we hypothesized that BC survivors might be prone to develop LC as a result of harboring rare variants. Sixty patients with LC with previous BC (the study population; SP) and 53 women with either BC or LC and no secondary cancer (control population; CP) were enrolled. Whole exome sequencing was performed in both tumors and unaffected tissues from 28/60 SP patients, and in germline DNA from 32/53 CP. Candidate genes were validated in the remaining individuals from both populations. We found two main mutational signature profiles: S1 (C>T) in all BCs and 16/28 LCs, and S2 (C>A) which is strongly associated with smoking, in 12/28 LCs. The burden test over rare germline variants in S1-LC vs CP identified 248 genes. Validation confirmed
Identifiants
pubmed: 30925779
pii: cancers11040441
doi: 10.3390/cancers11040441
pmc: PMC6520745
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Italian Ministry of Health
ID : GR 2011-12; 02350922
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