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Genetic alterations of triple negative breast cancer by targeted next-generation sequencing and correlation with tumor morphology #
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TNBC 39 사례의 normal-tumor pair를 229 cancer gene associated NGS Deep sequencing 함.

가장 많은 변이는

  1. TP53 (74%)
  2. PIK3CA (10%)
  3. MYC amplification (26%)

Apocrine 분화 관련 TNBC는 변이가 더 적음 (TP53 25%, MYC 0%) 대신 PICK3CA와 PI3K signaling pathway 관련 변이는 더 많음 (75%). 이는 luminal subtype과 유사함.

Summary #

Introduction #

TP53 변이 빈도는 TNBC에서만 높다. luminal에서는 PIK2CA.

MSK-IMPACT 플랫폼으로 NGS 타겟 시퀀싱. (229 common cancer genes)

Meterials and methods #

Patient Selection #

Clinicopathological Review #

Apocrine differentiation was defined as nuclear enlargement with prominent nucleoli and abundant, granular, eosinophilic cytoplasm.

Immunohistochemistry for Androgen Receptor #

DNA Extraction #

The MSK-IMPACT Assay #

Data were demultiplexed using CASAVA, and

  1. were aligned to reference (hg19) using BWA
  2. GATK best practice
  3. SNV by MuTech
  4. Indel by GATK SomaticIndenDetector
  5. Copy number by GATK DepthOfCoverage
  6. Integrated to IGV

Mutation Significance Analysis #

Functional effect of missense mutation using

Sanger Sequencing #

Statistical Analysis #

TCGA TNBC 데이터로 비교 (n=78)

Results #

Clinicopathologic Characteristics of the Patients #

Immunohistochemistry #

Somatic Mutations and Copy Number Alterations #

The average depth of sequencing was 678 (tumor), 348 (normal)

평균 변이 수는 3.33으로 TCGA 2.37 보다 유의하게 높다.

변이 유전자

  1. TP53
  2. MLL2
  3. PIK3CA

Genetic Alterations by Histologic Subtypes and Morphologic Features #

Triple Negative Breast Cancer Not Otherwise Specified #

Triple Negative Breast Cancer with Apocrine Differentiation #

4/39 (10%) is with apocrine differentiation.

  • older
  • average number of non-synonymous mutation

PIK3CA and NF1

Metaplastic Carcinoma #

Triple Negative Breast Cancer with a Large Central Acellular Zone #

Tumors with Prominent Tumor-infiltrating Lymphocytes #

Genetic Alterations in BRCA1 Germline Mutation Carriers #

Discussion #

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