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Exome sequencing in a breast cancer family without BRCA mutation.

Noh JM, Kim J, Cho DY, Choi DH, Park W, Huh SJ - Radiat Oncol J (2015)

Bottom Line: After filtering out 12,843 synonymous variations and 12,105 known variations with indels found in the dbSNP135 or 1000 Genomes Project database, we selected 73 variations in the samples from the affected sisters that did not occur in the sample from the unaffected mother.Using the Sorting Intolerant From Tolerant (SIFT), PolyPhen-2, and MutationTaster algorithms to predict amino acid substitutions, the XCR1, DLL1, TH, ACCS, SPPL3, CCNF, and SRL genes were risky among all three algorithms, while definite candidate genes could not be conclusively determined.Genetic evidence of disease association should be confirmed by future studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

ABSTRACT

Purpose: We performed exome sequencing in a breast cancer family without BRCA mutations.

Materials and methods: A family that three sisters have a history of breast cancer was selected for analysis. There were no family members with breast cancer in the previous generation. Genetic testing for BRCA mutation was negative, even by the multiplex ligation-dependent probe amplification method. Two sisters with breast cancer were selected as affected members, while the mother of the sisters was a non-affected member. Whole exome sequencing was performed on the HiSeq 2000 platform with paired-end reads of 101 bp in the three members.

Results: We identified 19,436, 19,468, and 19,345 single-nucleotide polymorphisms (SNPs) in the coding regions. Among them, 8,759, 8,789, and 8,772 were non-synonymous SNPs, respectively. After filtering out 12,843 synonymous variations and 12,105 known variations with indels found in the dbSNP135 or 1000 Genomes Project database, we selected 73 variations in the samples from the affected sisters that did not occur in the sample from the unaffected mother. Using the Sorting Intolerant From Tolerant (SIFT), PolyPhen-2, and MutationTaster algorithms to predict amino acid substitutions, the XCR1, DLL1, TH, ACCS, SPPL3, CCNF, and SRL genes were risky among all three algorithms, while definite candidate genes could not be conclusively determined.

Conclusion: Using exome sequencing, we found 7 variants for a breast cancer family without BRCA mutations. Genetic evidence of disease association should be confirmed by future studies.

No MeSH data available.


Related in: MedlinePlus

The familial pedigree of the sequenced family. Three sisters had a history of breast cancer, while the second sister had simultaneous thyroid cancer. This sister received genetic testing for BRCA and BRAF mutations, and was positive for the BRAFV600E mutation, but negative for the BRCA mutation. There were no family members with breast or thyroid cancer in the previous generation.
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Figure 1: The familial pedigree of the sequenced family. Three sisters had a history of breast cancer, while the second sister had simultaneous thyroid cancer. This sister received genetic testing for BRCA and BRAF mutations, and was positive for the BRAFV600E mutation, but negative for the BRCA mutation. There were no family members with breast or thyroid cancer in the previous generation.

Mentions: A Korean family that three sisters have a history of breast cancer was selected for analysis (Fig. 1). The second sister had simultaneous breast and thyroid cancer, and another sister without breast cancer had a history of thyroid cancer. There were no members with breast or thyroid cancer in the previous generation. The second sister underwent genetic testing for BRCA and BRAF mutations and BRAFV600E mutation, a somatic mutation [13], was detected. However, no mutation was detected in the BRCA1 and BRCA2 genes, even by the multiplex ligation-dependent probe amplification method.


Exome sequencing in a breast cancer family without BRCA mutation.

Noh JM, Kim J, Cho DY, Choi DH, Park W, Huh SJ - Radiat Oncol J (2015)

The familial pedigree of the sequenced family. Three sisters had a history of breast cancer, while the second sister had simultaneous thyroid cancer. This sister received genetic testing for BRCA and BRAF mutations, and was positive for the BRAFV600E mutation, but negative for the BRCA mutation. There were no family members with breast or thyroid cancer in the previous generation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493427&req=5

Figure 1: The familial pedigree of the sequenced family. Three sisters had a history of breast cancer, while the second sister had simultaneous thyroid cancer. This sister received genetic testing for BRCA and BRAF mutations, and was positive for the BRAFV600E mutation, but negative for the BRCA mutation. There were no family members with breast or thyroid cancer in the previous generation.
Mentions: A Korean family that three sisters have a history of breast cancer was selected for analysis (Fig. 1). The second sister had simultaneous breast and thyroid cancer, and another sister without breast cancer had a history of thyroid cancer. There were no members with breast or thyroid cancer in the previous generation. The second sister underwent genetic testing for BRCA and BRAF mutations and BRAFV600E mutation, a somatic mutation [13], was detected. However, no mutation was detected in the BRCA1 and BRCA2 genes, even by the multiplex ligation-dependent probe amplification method.

Bottom Line: After filtering out 12,843 synonymous variations and 12,105 known variations with indels found in the dbSNP135 or 1000 Genomes Project database, we selected 73 variations in the samples from the affected sisters that did not occur in the sample from the unaffected mother.Using the Sorting Intolerant From Tolerant (SIFT), PolyPhen-2, and MutationTaster algorithms to predict amino acid substitutions, the XCR1, DLL1, TH, ACCS, SPPL3, CCNF, and SRL genes were risky among all three algorithms, while definite candidate genes could not be conclusively determined.Genetic evidence of disease association should be confirmed by future studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

ABSTRACT

Purpose: We performed exome sequencing in a breast cancer family without BRCA mutations.

Materials and methods: A family that three sisters have a history of breast cancer was selected for analysis. There were no family members with breast cancer in the previous generation. Genetic testing for BRCA mutation was negative, even by the multiplex ligation-dependent probe amplification method. Two sisters with breast cancer were selected as affected members, while the mother of the sisters was a non-affected member. Whole exome sequencing was performed on the HiSeq 2000 platform with paired-end reads of 101 bp in the three members.

Results: We identified 19,436, 19,468, and 19,345 single-nucleotide polymorphisms (SNPs) in the coding regions. Among them, 8,759, 8,789, and 8,772 were non-synonymous SNPs, respectively. After filtering out 12,843 synonymous variations and 12,105 known variations with indels found in the dbSNP135 or 1000 Genomes Project database, we selected 73 variations in the samples from the affected sisters that did not occur in the sample from the unaffected mother. Using the Sorting Intolerant From Tolerant (SIFT), PolyPhen-2, and MutationTaster algorithms to predict amino acid substitutions, the XCR1, DLL1, TH, ACCS, SPPL3, CCNF, and SRL genes were risky among all three algorithms, while definite candidate genes could not be conclusively determined.

Conclusion: Using exome sequencing, we found 7 variants for a breast cancer family without BRCA mutations. Genetic evidence of disease association should be confirmed by future studies.

No MeSH data available.


Related in: MedlinePlus