Abstract
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 GSN as significantly associated with LC in never-smokers. In conclusion, our data suggest two signatures involved in LC onset in women with previous BC. One of these signatures is linked to smoking. Conversely, regardless of smoking habit, in a subgroup of BC survivors genetic susceptibility may contribute to LC risk.
| Original language | English |
|---|---|
| Journal | Cancers |
| Volume | 11 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Mar 28 2019 |
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Integrated Somatic and Germline Whole-Exome Sequencing Analysis in Women with Lung Cancer after a Previous Breast Cancer. / Coco, Simona; Bonfiglio, Silvia; Cittaro, Davide; Vanni, Irene; Mora, Marco; Genova, Carlo; Dal Bello, Maria Giovanna; Boccardo, Simona; Alama, Angela; Rijavec, Erika; Sini, Claudio; Rossella, Valeria; Barletta, Giulia; Biello, Federica; Truini, Anna; Bruzzo, Cristina; Gallo, Maurizio; Lazarevic, Dejan; Ballestrero, Alberto; Grossi, Francesco.
In: Cancers, Vol. 11, No. 4, 28.03.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Integrated Somatic and Germline Whole-Exome Sequencing Analysis in Women with Lung Cancer after a Previous Breast Cancer
AU - Coco, Simona
AU - Bonfiglio, Silvia
AU - Cittaro, Davide
AU - Vanni, Irene
AU - Mora, Marco
AU - Genova, Carlo
AU - Dal Bello, Maria Giovanna
AU - Boccardo, Simona
AU - Alama, Angela
AU - Rijavec, Erika
AU - Sini, Claudio
AU - Rossella, Valeria
AU - Barletta, Giulia
AU - Biello, Federica
AU - Truini, Anna
AU - Bruzzo, Cristina
AU - Gallo, Maurizio
AU - Lazarevic, Dejan
AU - Ballestrero, Alberto
AU - Grossi, Francesco
PY - 2019/3/28
Y1 - 2019/3/28
N2 - 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 GSN as significantly associated with LC in never-smokers. In conclusion, our data suggest two signatures involved in LC onset in women with previous BC. One of these signatures is linked to smoking. Conversely, regardless of smoking habit, in a subgroup of BC survivors genetic susceptibility may contribute to LC risk.
AB - 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 GSN as significantly associated with LC in never-smokers. In conclusion, our data suggest two signatures involved in LC onset in women with previous BC. One of these signatures is linked to smoking. Conversely, regardless of smoking habit, in a subgroup of BC survivors genetic susceptibility may contribute to LC risk.
U2 - 10.3390/cancers11040441
DO - 10.3390/cancers11040441
M3 - Article
C2 - 30925779
VL - 11
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 4
ER -