Salivary Gland Cancer in<i>BRCA</i>-Positive Families

Shen, Tim K.; Teknos, Theodoros N.; Toland, Amanda E.; Senter, Leigha; Nagy, Rebecca

doi:10.1001/jamaoto.2014.1998

Cited by 23 publications

(11 citation statements)

References 10 publications

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“…We have provided the first report of a SDC patient harboring a germline BRCA1 E23fs mutation. A single previous study has shown that the prevalence of salivary carcinoma, being salivary gland carcinoma not otherwise specified and adenoid cystic carcinoma, among BRCA1-mutated probands and likely carriers is significantly higher than the background incidence rate (0.052% vs. 0.003%, p<0.001) [35]. However, possible associations between germline BRCA1/2 mutations and SDC in particular have not been previously reported.…”

Section: Discussionmentioning

confidence: 93%

The repertoire of genetic alterations in salivary duct carcinoma including a novel HNRNPH3-ALK rearrangement

Doğan

et al. 2019

Human Pathology

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Salivary duct carcinoma (SDC) is a rare, aggressive malignancy with limited treatment options and poor outcome. Twenty-nine primary resected SDC, including 15 SDC de novo (SDCDN), and 14 SDC ex pleomorphic adenoma (SDCXPA) were subjected to the massive parallel sequencing assay (MSK-IMPACT™) targeting 287-468 cancer-related genes. TP53 was the most frequently altered gene (69%). TP53 mutations and ERBB2 amplification were more frequent in SDCXPA than in SDCDN (p=0.0007 and p=0.01, respectively). Potentially targetable mutations were detected in 79% (23/29) SDC involving ERBB2 (31%), PIK3CA (28%), HRAS (21%), ALK (7%) and BRAF (3%), and 22% (5/23) of those cases harbored possible primary resistance mutations involving CCNE1, NF1 and PTEN. A novel HNRNPH3-ALK rearrangement was found in one SDCDN. In another case, EML4-ALK fusion detected in the primary tumor was associated with ALK G1202R secondary resistance mutation in the post-treatment metastasis. A germline analysis of the DNA repair genes revealed a case with a pathogenic BRCA1 E23fs germline variant.

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Section: Discussionmentioning

confidence: 93%

The repertoire of genetic alterations in salivary duct carcinoma including a novel HNRNPH3-ALK rearrangement

Doğan

et al. 2019

Human Pathology

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“…Germline mutations that could account for the occurrence of both a salivary gland tumor and BC in the same woman have not been identified yet, and the literature on this topic is limited. One retrospective study including 5754 proven or likely carriers from 187 BRCA1 or BRCA2 positive pedigrees, reported three SGCs 59 . Although the authors reported an increased SGC incidence, a 95% CI was not provided.…”

Section: Discussionmentioning

confidence: 99%

Risk of breast cancer in women after a salivary gland carcinoma or pleomorphic adenoma in the Netherlands

Valstar

Schaapveld

Broek³

et al. 2020

Cancer Medicine

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Salivary and mammary gland tumors show morphological similarities and share various characteristics, including frequent overexpression of hormone receptors and female preponderance. Although this may suggest a common etiology, it remains unclear whether patients with a salivary gland tumor carry an increased risk of breast cancer (BC). Our purpose was to determine the risk of BC in women diagnosed with salivary gland carcinoma (SGC) or pleomorphic adenoma (SGPA). BC incidence (invasive and in situ) was assessed in two nationwide cohorts: one comprising 1567 women diagnosed with SGC and one with 2083 women with SGPA. BC incidence was compared with general population rates using standardized incidence ratio (SIR). BC risk was assessed according to age at SGC/SGPA diagnosis, follow‐up time and (for SGC patients) histological subtype. The mean follow‐up was 7.0 years after SGC and 9.9 after SGPA diagnosis. During follow‐up, 52 patients with SGC and 74 patients with SGPA developed BC. The median time to BC was 6 years after SGC and 7 after SGPA. The cumulative risk at 10 years of follow‐up was 3.1% after SGC and 3.5% after SGPA (95% Confidence Interval (95%CI) 2.1%–4.7% and 2.6%–4.6%, respectively). BC incidence was 1.59 times (95%CI 1.19–2.09) higher in the SGC‐cohort than expected based on incidence rates in the general population. SGPA‐patients showed a 1.48 times (95%CI 1.16–1.86) higher incidence. Women with SGC or SGPA have a slightly increased risk of BC. The magnitude of risk justifies raising awareness, but is no reason for BC screening.

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“…Additionally, breast and salivary glands are known to share many morphological features, and studies have shown that both can give rise to tumors with similar morphology [ 118 , 119 ] and myoepithelial differentiation [ 120 ]. These finding can explain why breast and salivary glands clustered with epithelial and myoepithelial cells, as opposed to glandular cells.…”

Section: Discussionmentioning

confidence: 99%

Reconstruction of Tissue-Specific Metabolic Networks Using CORDA

2016

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Human metabolism involves thousands of reactions and metabolites. To interpret this complexity, computational modeling becomes an essential experimental tool. One of the most popular techniques to study human metabolism as a whole is genome scale modeling. A key challenge to applying genome scale modeling is identifying critical metabolic reactions across diverse human tissues. Here we introduce a novel algorithm called Cost Optimization Reaction Dependency Assessment (CORDA) to build genome scale models in a tissue-specific manner. CORDA performs more efficiently computationally, shows better agreement to experimental data, and displays better model functionality and capacity when compared to previous algorithms. CORDA also returns reaction associations that can greatly assist in any manual curation to be performed following the automated reconstruction process. Using CORDA, we developed a library of 76 healthy and 20 cancer tissue-specific reconstructions. These reconstructions identified which metabolic pathways are shared across diverse human tissues. Moreover, we identified changes in reactions and pathways that are differentially included and present different capacity profiles in cancer compared to healthy tissues, including up-regulation of folate metabolism, the down-regulation of thiamine metabolism, and tight regulation of oxidative phosphorylation.

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Salivary Gland Cancer inBRCA-Positive Families

Abstract: We believe this is a significant observation that, when considered alongside other similarities between salivary glands and breast tissue, warrants further investigation into the nature of a possible linkage between germline BRCA mutations and salivary gland cancer.

Cited by 23 publications

References 10 publications

The repertoire of genetic alterations in salivary duct carcinoma including a novel HNRNPH3-ALK rearrangement

The repertoire of genetic alterations in salivary duct carcinoma including a novel HNRNPH3-ALK rearrangement

Risk of breast cancer in women after a salivary gland carcinoma or pleomorphic adenoma in the Netherlands

Reconstruction of Tissue-Specific Metabolic Networks Using CORDA

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