Expression and mutational status of treatment-relevant targets and key oncogenes in 123 malignant salivary gland tumours

Cros, Jérôme; Sbidian, É.; Hans, Stéphane; Roussel, H.; Scotte, F.; Tartour, Éric; Brasnu, Daniel; Laurent‐Puig, Pierre; Bruneval, P; Blons, Hélène; Badoual, Cécile

doi:10.1093/annonc/mdt338

Cited by 79 publications

(64 citation statements)

References 15 publications

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“…ERBB2 mutations were previously reported in SDC. [12][13][14] Other tested mutation hotspots in genes listed below were negative: ABL1, AKT1, ALK, APC, ATM, CDH1, CSF1R, CTNNB1, EGFR, ERBB4, EZH2, FGFR1, The presumably functional mutations in APC or CTNNB1 would lead to nuclear translocation of b-catenin. In agreement with NGS results, IHC for b-catenin performed on all 30 SDCs showed no nuclear b-catenin staining.…”

Section: Pik3ca Hras and Other Mutationsmentioning

confidence: 99%

“…[6][7][8] Recently, additional potentially targetable genetic abnormalities in SDC were identified, including mutations of the gene encoding the p110a catalytic subunit of phosphoinositide 3-kinase (PIK3CA), 9,10 PTEN deletion, 11 and occasional BRAF or ERBB2 (HER2) mutations. [12][13][14] Nonetheless, the prevalence of genetic changes in these and potentially other genes and the relationship between genetic changes and clinicopathologic features of SDC are unknown. As an example, it is possible that the origin of SDC (de novo vs. ex pleomorphic adenoma [PA]) or androgen receptor (AR) status may affect the prevalence of genetic alterations.…”

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confidence: 99%

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Molecular Characterization of Apocrine Salivary Duct Carcinoma

Chiosea

Williams

Griffith

et al. 2015

American Journal of Surgical Pathology

115

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Contemporary classification and treatment of salivary duct carcinoma (SDC) require its thorough molecular characterization. Thirty apocrine SDCs were analyzed by the Ion Ampliseq Cancer HotSpot panel v2 for mutations in 50 cancer-related genes. Mutational findings were corroborated by immunohistochemistry (eg, TP53, BRAF, β-catenin, estrogen, and androgen receptors) or Sanger sequencing/SNaPshot polymerase chain reaction. ERBB2 (HER2), PTEN, FGFR1, CDKN2A/P16, CMET, EGFR, MDM2, and PIK3CA copy number changes were studied by fluorescence in situ hybridization. TP53 mutations (15/27, 56%), PTEN loss (11/29, 38%, including 2 cases with PTEN mutation), PIK3CA hotspot mutations (10/30, 33%), HRAS hotspot mutations (10/29; 34%), and ERBB2 amplification (9/29, 31%, including 1 case with mutation) represented the 5 most common abnormalities. There was no correlation between genetic changes and clinicopathologic parameters. There was substantial overlap between genetic changes: 8 of 9 cases with ERBB2 amplification also harbored a PIK3CA, HRAS, and TP53 mutation and/or PTEN loss. Six of 10 cases with PIK3CA mutation also had an HRAS mutation. These findings provide a molecular rationale for dual targeting of mitogen-activated protein kinase and phosphoinositide 3-kinase pathways in SDC. FGFR1 amplification (3/29, 10%) represents a new potential target. On the basis of studies of breast carcinomas, the efficacy of anti-ERBB2 therapy will likely be decreased in SDC with ERBB2 amplification co-occurring with PIK3CA mutation or PTEN loss. Therefore, isolated ERBB2 testing is insufficient for theranostic stratification of apocrine SDC. On the basis of the prevalence and type of genetic changes, apocrine SDC appears to resemble one subtype of breast carcinoma-"luminal androgen receptor positive/molecular apocrine."

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Section: Pik3ca Hras and Other Mutationsmentioning

confidence: 99%

mentioning

confidence: 99%

Molecular Characterization of Apocrine Salivary Duct Carcinoma

Chiosea

Williams

Griffith

et al. 2015

American Journal of Surgical Pathology

115

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“…Another study indicated that, as a multi-cell hybrid myoepithelioma, the cytoplasmic mucin content was the important feature of myoepithelioma (11). Cros et al (12) studied the treatment-associated gene mutations and target expressions of 123 patients with malignant salivary gland tumors, and revealed that 107 patients had varied gene mutations and target expressions, which provided the basis for additional molecular targeted therapy.…”

Section: Discussionmentioning

confidence: 99%

Recurrent myoepithelial carcinoma of the submandibular gland treated by rAd-p53 combined with radiotherapy: A case report

et al. 2016

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Abstract. The aim of the present study was to report the case of a patient with recurrent myoepithelial carcinoma of the submandibular gland without progression for five years following treatment. A 71-year-old male patient presented to hospital with a painless swelling in the region of the right submandibular gland, and received a radical neck dissection on January 29, 2008. A nodule of ~7x4x2 cm was identified at the site of the right submandibular gland, and the pathological results revealed a diagnosis of myoepithelial carcinoma of the right submandibular gland with no lymph node metastasis. However, this case developed local recurrence with wide-spread metastasis in the lungs. Between April and October 2008, the patient underwent several treatment regimens and demonstrated no improvement following 6 cycles of chemotherapy. From then on, the patient was treated with recombinant adenoviral-p53 (rAd-p53) combined with radiotherapy using a 6 millivolt medical linear accelerator. The foci were relieved and the cancer demonstrated no signs of progression during the 5-year follow-up. rAd-p53 combined with radiotherapy was useful for treating myoepithelial carcinoma of the submandibular gland.

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“…No PTEN mutation was observed, in keeping with a recent study. 9 Notably, R175 TP53 mutation leads to a "non-functional" p53 protein lacking transcriptional activity. 8 Abrogation of p53 function could have a relevant implications in AR expression regulation: it has been demonstrated that p53 wild type inhibits AR transcription 10 and the removal of the negative regulation of AR could lead to an AR overexpression.…”

Section: Discussionmentioning

confidence: 99%

“…Silencing of PI3K/AKT pathway might also counteract signals from activating mutation of PIK3CA accounting for 5% of SGCs. 9 In case 2, we also analyzed the bone metastasis developed during CAB, in order to identify biomarkers potentially related to resistance to ADT such as AR mutation/amplification and PI3K/PTEN mutation pathway, 14 whereas due to the exiguity of the FFPE material we were not able to investigate PTEN loss, recently reported in AR-positive SDCs. 15 Primary tumor and metastatic bone lesion presented the same immunohistochemical, cytogenetic, and molecular profile, suggesting that secondary hormone resistance mechanisms require further investigations in AR-positive SGCs.…”

mentioning

confidence: 99%