摘要
Although somatic mutations are the main cause of cancer, underlying germline alterations may affect cancer outcome. There is little information on comprehensive analysis of germline genome sequencing for cancer healthcare strategy. Here we studied the implication of germline cancer-associated variants on cancer counselling and therapeutic strategies by germline whole genome and tumor targeted sequencing. Fifty-five gynecological and 104 colorectal cancer (CRC) patients were enrolled. We identified 22 germline pathogenic variants in 16 cancer-associated genes. Most of them are involved in DNA repair signaling, including MLH1, BRCA1/2, MUTYH, ATM, PMS2, MSH6, BAP1, and FANCA. About 6% of cancer patients presented the secondary findings of germline variants with non-oncogenic impact, mainly on the cardiovascular system which should be carefully monitored during chemotherapy. CRC patients carrying germline susceptibility variants had better disease-free survival than those without variants. Importantly, in the CRC model, the underlying germline alterations mold the tumor somatic alteration landscape. NOTCH1 mutation was the most common somatic mutation in recurrent CRC, implying a potential therapeutic target in adjuvant setting. In conclusion, both tumor genome and germline sequence data have to be analyzed to have a more complete picture of the overall genetic foundation of cancer.
| 原文 | English |
|---|---|
| 文章編號 | 3931 |
| 期刊 | Scientific reports |
| 卷 | 9 |
| 發行號 | 1 |
| DOIs | |
| 出版狀態 | Published - 2019 十二月 1 |
指紋
All Science Journal Classification (ASJC) codes
- General
引用此文
}
TY - JOUR
T1 - Germline susceptibility variants impact clinical outcome and therapeutic strategies for stage III colorectal cancer
AU - Lin, Peng-Chan
AU - Yeh, Yu-Min
AU - Wu, Pei-Ying
AU - Hsu, Keng-Fu
AU - Chang, Jang-Yang
AU - Shen, Meng-Ru
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Although somatic mutations are the main cause of cancer, underlying germline alterations may affect cancer outcome. There is little information on comprehensive analysis of germline genome sequencing for cancer healthcare strategy. Here we studied the implication of germline cancer-associated variants on cancer counselling and therapeutic strategies by germline whole genome and tumor targeted sequencing. Fifty-five gynecological and 104 colorectal cancer (CRC) patients were enrolled. We identified 22 germline pathogenic variants in 16 cancer-associated genes. Most of them are involved in DNA repair signaling, including MLH1, BRCA1/2, MUTYH, ATM, PMS2, MSH6, BAP1, and FANCA. About 6% of cancer patients presented the secondary findings of germline variants with non-oncogenic impact, mainly on the cardiovascular system which should be carefully monitored during chemotherapy. CRC patients carrying germline susceptibility variants had better disease-free survival than those without variants. Importantly, in the CRC model, the underlying germline alterations mold the tumor somatic alteration landscape. NOTCH1 mutation was the most common somatic mutation in recurrent CRC, implying a potential therapeutic target in adjuvant setting. In conclusion, both tumor genome and germline sequence data have to be analyzed to have a more complete picture of the overall genetic foundation of cancer.
AB - Although somatic mutations are the main cause of cancer, underlying germline alterations may affect cancer outcome. There is little information on comprehensive analysis of germline genome sequencing for cancer healthcare strategy. Here we studied the implication of germline cancer-associated variants on cancer counselling and therapeutic strategies by germline whole genome and tumor targeted sequencing. Fifty-five gynecological and 104 colorectal cancer (CRC) patients were enrolled. We identified 22 germline pathogenic variants in 16 cancer-associated genes. Most of them are involved in DNA repair signaling, including MLH1, BRCA1/2, MUTYH, ATM, PMS2, MSH6, BAP1, and FANCA. About 6% of cancer patients presented the secondary findings of germline variants with non-oncogenic impact, mainly on the cardiovascular system which should be carefully monitored during chemotherapy. CRC patients carrying germline susceptibility variants had better disease-free survival than those without variants. Importantly, in the CRC model, the underlying germline alterations mold the tumor somatic alteration landscape. NOTCH1 mutation was the most common somatic mutation in recurrent CRC, implying a potential therapeutic target in adjuvant setting. In conclusion, both tumor genome and germline sequence data have to be analyzed to have a more complete picture of the overall genetic foundation of cancer.
UR - http://www.scopus.com/inward/record.url?scp=85062644154&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062644154&partnerID=8YFLogxK
U2 - 10.1038/s41598-019-40571-0
DO - 10.1038/s41598-019-40571-0
M3 - Article
C2 - 30850667
AN - SCOPUS:85062644154
VL - 9
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 3931
ER -