Abstract P6-18-01: Novel genetic susceptibility loci for inflammatory breast cancer identified by whole exome sequencing

AbstractInflammatory breast cancer (IBC) is the most aggressive form of breast cancer. Although it is a rare subtype, IBC is responsible for roughly 10% of breast cancer deaths. In order to obtain a better understanding of the genomic landscape and intratumor heterogeneity (ITH) in IBC, we conducted whole-exome sequencing of 16 tissue samples (12 tumor and four normal samples) from six hormone-receptor-positive IBC patients, analyzed somatic mutations and copy number aberrations, and inferred subclonal structures to demonstrate ITH. Our results showed that KMT2C was the most frequently mutated gene (42%, 5/12 samples), followed by HECTD1, LAMA3, FLG2, UGT2B4, STK33, BRCA2, ACP4, PIK3CA, and DNAH8 (all nine genes tied at 33% frequency, 4/12 samples). Our data indicated that PTEN and FBXW7 mutations may be considered driver gene mutations for IBC. We identified various subclonal structures and different levels of ITH between IBC patients, and mutations in the genes EIF4G3, IL12RB2, and PDE4B may potentially generate ITH in IBC.

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Searching for the missing genetic determinants of hereditary breast cancer risk by whole-exome sequencing of BRCA-negative patients: new candidate genes USP39, SLIT3, CREB3

Problems in oncology ◽

10.37469/0507-3758-2021-67-1-111-116 ◽

2021 ◽

Vol 67 (1) ◽

pp. 111-116

Author(s):

Kirill Zagorodnev ◽

Aleksandr Romanko ◽

Uliy Gorgul ◽

Aleksandr Ivantsov ◽

Anna Sokolenko ◽

...

Keyword(s):

Breast Cancer ◽

Exome Sequencing ◽

Candidate Genes ◽

Whole Exome Sequencing ◽

Hereditary Breast Cancer ◽

Germ Line ◽

Genetic Diagnosis ◽

Clinical Signs ◽

Causative Mutation ◽

Whole Exome

The search for the new hereditary mutations and a precise molecular genetic diagnosis that determines the causative mutation in each specific case of hereditary breast cancer (BC) is a clinically important task since it helps to define the personal therapeutic approach and increase the effectiveness of preventive measures. Using whole-exome sequencing (WES) we analyzed the full spectrum of hereditary variations in 49 Russian patients with clinical signs of a hereditary disease which allowed us to compile a list of 229 candidate probably pathogenic germ-line variants. Then, the selected candidate mutations were validated by Sanger sequencing and molecular-epidemiological studies, the predisposing roles of three oncologically relevant mutations (USP39 c.*208G>C, SLIT3 p.Arg154Cys, and CREB3 p.Lys157Glu) were confirmed. Our candidate genes are first mentioned in connection with the hereditary risk of BC. The final proofs of the causative roles of these variants could be obtained through functional tests as well as via the analysis of the mutations segregation in BC families.

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Pioneering Informed Consent for Return of Research Results to Breast Cancer Patients Facing Barriers to Implementation of Genomic Medicine: The Kenyan BRCA1/2 Testing Experience Using Whole Exome Sequencing

Frontiers in Genetics ◽

10.3389/fgene.2020.00170 ◽

2020 ◽

Vol 11 ◽

Author(s):

Rispah Torrorey-Sawe ◽

Nicole van der Merwe ◽

Simeon Kipkoech Mining ◽

Maritha J. Kotze

Keyword(s):

Breast Cancer ◽

Informed Consent ◽

Exome Sequencing ◽

Cancer Patients ◽

Whole Exome Sequencing ◽

Genomic Medicine ◽

Breast Cancer Patients ◽

Whole Exome ◽

Barriers To Implementation ◽

Return Of Research Results

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Whole-exome sequencing of long-term, never relapse exceptional responders of trastuzumab-treated HER2+ metastatic breast cancer

British Journal of Cancer ◽

10.1038/s41416-020-0999-z ◽

2020 ◽

Vol 123 (8) ◽

pp. 1219-1222

Author(s):

Naomi Walsh ◽

Charlotte Andrieu ◽

Peter O’Donovan ◽

Cecily Quinn ◽

Alanna Maguire ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Metastatic Breast ◽

Whole Exome

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Abstract LB-343: Defining mechanisms of endocrine resistance in breast cancer using whole exome sequencing

10.1158/1538-7445.am2012-lb-343 ◽

2012 ◽

Author(s):

Natasha Chandiramani ◽

Kelly S. Levano ◽

Esther A. Peterson ◽

Paraic A. Kenny

Keyword(s):

Breast Cancer ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Endocrine Resistance ◽

Whole Exome

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Abstract P4-14-01: Whole exome sequencing reveals greater intratumor genetic heterogeneity in primary breast cancer arising in African American compared to Caucasian women

10.1158/1538-7445.sabcs14-p4-14-01 ◽

2015 ◽

Author(s):

Tanya E Keenan ◽

Edmund A Mroz ◽

James W Rocco ◽

Leif W Ellisen ◽

Beverly Moy ◽

...

Keyword(s):

Breast Cancer ◽

African American ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Genetic Heterogeneity ◽

Primary Breast Cancer ◽

Whole Exome ◽

Caucasian Women

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Integrated Somatic and Germline Whole-Exome Sequencing Analysis in Women with Lung Cancer after a Previous Breast Cancer

Cancers ◽

10.3390/cancers11040441 ◽

2019 ◽

Vol 11 (4) ◽

pp. 441 ◽

Cited By ~ 1

Author(s):

Simona Coco ◽

Silvia Bonfiglio ◽

Davide Cittaro ◽

Irene Vanni ◽

Marco Mora ◽

...

Keyword(s):

Breast Cancer ◽

Lung Cancer ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Smoking Habit ◽

Cancer Control ◽

Sequencing Analysis ◽

Multiple Cancer ◽

Germline Variants ◽

Whole Exome

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.

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