The repertoire of somatic genetic alterations of acinic cell carcinomas of the breast: an exploratory, hypothesis‐generating study

Guerini-Rocco, Elena; Hodi, Zsolt; Piscuoglio, Salvatore; Ng, Charlotte K.Y.; Rakha, Emad A.; Schultheis, Anne M.; Marchiò, Caterina; Paula, Arnaud Da Cruz; Filippo, Maria Rosaria De; Martelotto, Luciano G.; Mattos-Arruda, Leticia De; Edelweiss, Marcia; Jungbluth, Achim A.; Fusco, Nicola; Norton, Larry; Weigelt, Britta; Ellis, Ian O.; Reis‐Filho, Jorge S.

doi:10.1002/path.4566

Cited by 56 publications

(96 citation statements)

References 67 publications

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“…In contrast, Piscuoglio et al [27] did not detect any mutations in TP53 in 20 salivary AcCCs, leading those authors to conclude that from a molecular pathology standpoint, breast AcCCs have far more in common with TNBC than salivary AcCCs. In keeping with these results, Guerini-Rocco et al [31] recently performed massively parallel sequencing analysis of the same cohort of breast AcCCs as Piscuoglio et al [27] and demonstrated a pattern of complex copy number aberrations that also mirrors that seen in TNBC. MLL3 , another likely oncogenic driver in our case, was also mutated in 7% of cases in the breast carcinoma/The Cancer Genome Atlas study [30], making it one of the top five most frequently mutated genes.…”

Section: Discussionmentioning

confidence: 78%

Acinic cell carcinoma of breast: morphologic and immunohistochemical review of a rare breast cancer subtype

et al. 2016

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Summary Acinic cell carcinoma of breast is a rare subtype of triple-negative breast carcinoma and demonstrates extensive morphologic overlap with acinic cell carcinoma of the salivary gland. In this study, we perform a detailed morphologic and immunohistochemical description of 2 cases of this rare entity and undertake a comprehensive review of all reported cases of breast acinic cell carcinoma in the English language literature to date. One-third of reported cases of breast acinic cell carcinoma have been associated with the presence of a ductal carcinoma not otherwise specified component, which is frequently poorly differentiated. Breast acinic cell carcinoma can demonstrate focal morphologic features similar to microglandular adenosis; these areas are frequently negative for collagen IV and laminin on immunohistochemistry. The true relationship between these 2 entities remains unclear, but we advocate that microglandular adenosis–like areas at the periphery of a breast acinic cell carcinoma should be considered part of the carcinomatous process and re-excised if this process extends to the initial surgical margins.

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Section: Discussionmentioning

confidence: 78%

Acinic cell carcinoma of breast: morphologic and immunohistochemical review of a rare breast cancer subtype

et al. 2016

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“…Immunohistochemical profile of the included cases (n=59) was assessed on 4μm-thick sections, using antibodies against ER, progesterone receptor (PR), HER2 and Ki-67 as previously described (23). Positive and negative controls were included in each experiment.…”

Section: Methodsmentioning

confidence: 99%

“…Custom oligonucleotides (NimblegenSeqCap) were designed for hybridization capture of the 241 genes (Supplementary Table S3) (28). Barcoded sequencing libraries were prepared (New England Biolabs) using 50ng to 250ng DNA and pooled at equimolar concentrations into a single capture reaction as previously described (23, 28). Paired-end 76bp reads were generated on the Illumina HiSeq2000.…”

Section: Methodsmentioning

confidence: 99%

The Genomic Landscape of Male Breast Cancers

Piscuoglio

Murray

et al. 2016

Clinical Cancer Research

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Purpose Male breast cancer (MaBC) is rare and its genomic landscape has yet to be fully characterized. Lacking studies in men, treatment of MaBC patients is extrapolated from results in females with the disease (FBC). We sought to define whether MaBCs harbor somatic genetic alterations in genes frequently altered in FBCs. Experimental Design All MaBCs were estrogen receptor-positive and all but two were HER2 negative. 59 MaBCs were subtyped by immunohistochemistry and tumor-normal pairs were microdissected and subjected to massively parallel sequencing targeting all exons of 241 genes frequently mutated in FBCs or DNA-repair related. The repertoires of somatic mutations and copy number alterations of MaBCs were compared to that of subtype-matched FBCs. Results 29% and 71% of MaBCs were immunohistochemically classified as luminal A-like or luminal B-like, respectively. MaBCs displayed a heterogeneous repertoire of somatic genetic alterations that to some extent recapitulated that of estrogen receptor (ER)-positive/HER2-negative FBCs, including recurrent mutations affecting PIK3CA (20%) and GATA3 (15%). ER-positive/HER2-negative MaBCs, however, less frequently harbored 16q losses, and PIK3CA and TP53 mutations than ER-positive/HER2-negative FBCs. In addition, MaBCs were found to be significantly enriched for mutations affecting DNA repair-related genes. Conclusion MaBCs less frequently harbor somatic genetic alterations typical of ER-positive/HER2-negative FBCs, such as PIK3CA and TP53 mutations and losses of 16q, suggesting that at least a subset of MaBCs are driven by a distinct repertoire of somatic changes. Given the genomic differences, caution may be needed in the application of biological and therapeutic findings from studies of FBCs to MaBCs.

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“…Furthermore, the normal tissue was microdissected to be devoid of any neoplastic cells as previously described. 29,30 Genomic DNA from each tumor component and matched normal tissue was extracted using the DNeasy Blood & Tissue Kit (Qiagen), according to the manufacturer’s instructions, and quantified using the Qubit 2.0 Fluorometer (Invitrogen, Life Technologies).…”

Section: Methodsmentioning

confidence: 99%

Genetic events in the progression of adenoid cystic carcinoma of the breast to high-grade triple-negative breast cancer

et al. 2016

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Adenoid cystic carcinoma of the breast is a rare histologic type of triple-negative breast cancer with an indolent clinical behavior, often driven by the MYB-NFIB fusion gene. Here we sought to define the repertoire of somatic genetic alterations in two adenoid cystic carcinomas associated with high-grade triple-negative breast cancer. The different components of each case were subjected to copy number profiling and massively parallel sequencing targeting all exons and selected regulatory and intronic regions of 488 genes. Reverse transcription PCR and fluorescence in situ hybridization were employed to investigate the presence of the MYB-NFIB translocation. The MYB-NFIB fusion gene was detected in both adenoid cystic carcinomas and their associated high-grade triple-negative breast cancer components. Whilst the distinct components of both cases displayed similar patterns of gene copy number alterations, massively parallel sequencing analysis revealed intra-tumor genetic heterogeneity. In case 1, progression from the trabecular adenoid cystic carcinoma to the high-grade triple-negative breast cancer was found to involve clonal shifts with enrichment of mutations affecting EP300, NOTCH1, ERBB2 and FGFR1 in the high-grade triple-negative breast cancer. In case 2, a clonal KMT2C mutation was present in the cribriform adenoid cystic carcinoma, solid adenoid cystic carcinoma and high-grade triple-negative breast cancer components, whereas a mutation affecting MYB was present only in the solid and high-grade triple-negative breast cancer areas and additional three mutations targeting STAG2, KDM6A and CDK12 were restricted to the high-grade triple-negative breast cancer. In conclusion, adenoid cystic carcinomas of the breast with high-grade transformation are underpinned by MYB-NFIB fusion gene, and, akin to other forms of cancer, may be constituted by a mosaic of cancer cell clones at diagnosis. The progression from adenoid cystic carcinoma to high-grade triple-negative breast cancer of no special type may involve the selection of neoplastic clones and/ or the acquisition of additional genetic alterations.

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The repertoire of somatic genetic alterations of acinic cell carcinomas of the breast: an exploratory, hypothesis‐generating study

Cited by 56 publications

References 67 publications

Acinic cell carcinoma of breast: morphologic and immunohistochemical review of a rare breast cancer subtype

Acinic cell carcinoma of breast: morphologic and immunohistochemical review of a rare breast cancer subtype

The Genomic Landscape of Male Breast Cancers

Genetic events in the progression of adenoid cystic carcinoma of the breast to high-grade triple-negative breast cancer

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