Hotspot activating PRKD1 somatic mutations in polymorphous low-grade adenocarcinomas of the salivary glands

Weinreb, Ilan; Piscuoglio, Salvatore; Martelotto, Luciano G.; Waggott, Daryl; Ng, Charlotte K.Y.; Perez-Ordonez, Bayardo; Harding, Nicholas J.; Alfaro, Javier A.; Chu, Kenneth C.; Viale, Agnès; Fusco, Nicola; Paula, Arnaud Da Cruz; Marchiò, Caterina; Sakr, Rita A.; Lim, Raymond S.; Thompson, Lester D.�R.; Chiosea, Simion I.; Seethala, Raja R.; Skálová, Alena; Stelow, Edward B.; Fonseca, Isabel; Assaad, Adel; How, Christine; Wang, Jianxin; Borja, Richard de; Chan-Seng-Yue, Michelle; Howlett, Christopher J.; Nichols, Anthony C.; Ye, Wen; Katabi, Nora; Buchner, Nicholas; Mullen, Laura; Kislinger, Thomas; Wouters, Bradly G.; Liu, Fei‐Fei; Norton, Larry; Mcpherson, John Douglas; Rubin, Brian P.; Clarke, Blaise A.; Weigelt, Britta; Boutros, Paul C.; Reis‐Filho, Jorge S.

doi:10.1038/ng.3096

Cited by 195 publications

(226 citation statements)

References 55 publications

(4 reference statements)

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“…d Tumor cells are similarly monomorphic and ductal, but contain slightly larger nuclei and more markedly cleared chromatin remincent of (classic) papillary thyroid carcinoma nuclei 80% of cases with CAMSG morphology, and in less than 10% of cases with classic PAC morphology [42]. In contrast, PRKD1 E710D mutations are largely restricted to classic PAC, with only about 10% of CAMSG type tumors showing a mutation [43,44]. The counterpoints to these arguments are that the findings in the literature are numerically insufficient, there is still some morphologic and genotypic overlap, and despite the regional aggressiveness, survival differences have not yet been established.…”

Section: Polymorphous Adenocarcinomamentioning

confidence: 99%

See 1 more Smart Citation

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Tumors of the Salivary Gland

Seethala

Stenman

2017

Head and Neck Pathol

345

302

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Section: Polymorphous Adenocarcinomamentioning

confidence: 99%

“…Key molecular alterations in salivary gland tumors are summarized in Table 1 [4,[42][43][44][64][65][66][67][68]. Of these the majority are mentioned in the new edition of this chapter.…”

Section: Key Molecular Alterationsmentioning

confidence: 99%

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Tumors of the Salivary Gland

Seethala

Stenman

2017

Head and Neck Pathol

345

302

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“…Nevertheless, in a recent multicenter study the authors found a number of cases with overlapping or unusual morphology [11]. PRKD1 activating hot-spot mutation encoding p.Glu710Asp was found to be specific for PLGA and might be useful as an ancillary diagnostic marker to differentiate PLGA from other salivary gland tumors [18]. Moreover, Weinreb et al found that 75% of cases (15/20) of CAMSGs harbor recurrent translocations in the PRKD gene family [11].…”

Section: Discussionmentioning

confidence: 99%

Giant cribriform adenocarcinoma of the tongue showing PRKD3 rearrangement

Majewska

Skálová²,

Weinreb³

et al. 2016

pjp

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Cribriform adenocarcinoma of the tongue and minor salivary glands (CAMSG) was first described 16 years ago. It typically presents as a mass at the base of the tongue with early spread to lymph nodes, but without potential for distant metastases. In the 2005 World Health Organization Classification of Tumors the entity was classified as a possible variant of polymorphous low-grade adenocarcinoma (PLGA). Since then, more than 40 cases have been described in the English literature. Recently, PRKD1-3 translocation was found in more than 80% of CAMSGs. In some of those cases ARID1A or DDX3X was the translocation partner. We reviewed 183 primary carcinomas of major and minor salivary glands, resected at the Medical University of Gdańsk, Poland, in the period 1992-2012, and identified only one case of CAMSG. A giant tumor developed at the base of the tongue in a 76-year-old man. The primary tumor was resected with multiple bilateral cervical lymph node metastases. The patient received radiotherapy but died 10 months after the surgery due to causes not related to the primary cancer. The tumor presented PRKD3 rearrangement as confirmed by FISH. As the tumor is extremely rare (it represented only 0.5% of salivary gland tumors in our series), the controversy on its nosological status is still unresolved. This is the first report in the world literature of a patient who died in the course of CAMSG.

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“…PLGA may be locally invasive, for example, palatal lesions will eventually invade the adjacent maxillary bone and sinuses [19]. Regional lymph node metastasis has been reported as high as 29%, but there is rarely hematogenous spread [26][27][28]. However, distant metastasis have reportedly been found in the lung and abdomen [29].…”

Section: Clinical Featuresmentioning

confidence: 99%

“…Furthermore, ARID1A has already been identified to have a role in gynecologic malignancies [26]. The PRKD1 gene encodes a kinase protein, which has been implicated in a variety of malignant processes, including: colorectal, breast, esophageal, laryngeal, and others [26,27,37]. Moreover, PRDK1 kinases partake in signal transduction, trafficking, migration, differentiation and proliferation of cells, as well as cell adhesion [28,37].…”

Section: Arid1a-prkd1 and Ddx3x-prkd1mentioning

confidence: 99%

Expression of Human Tissue Kallikreins (KLKs) in Polymorphous Low Grade Adenocarcinoma (PLGA)

Cox

2014

Journal of Oral and Maxillofacial Surgery

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Polymorphous low grade adenocarcinoma (PLGA) is the second most common malignant salivary gland tumour of the minor salivary glands. Human tissue kallikreins (KLKs) are a family of highly conserved serine proteases expressed by various tissues throughout the body. KLKs have become powerful tumour markers for the diagnosis of the cancer patient (e.g. PSA (KLK3)). The literature demonstrates a link between KLKs and salivary gland neoplasms. The purpose of this study is to determine levels of KLK mRNA in tissue samples of formalin fixed paraffin embedded polymorphous low grade adenocarcinoma (PLGA). Secondly, we wish to determine if KLK expression is limited to tumour cells alone.Nineteen cases of PLGA were reviewed . A diagnosis of PLGA was confirmed, demographic data was collected, and formalin fixed paraffin-embedded PLGA and normal salivary gland tissue samples were obtained. RNA isolation was achieved, followed by conversion to complementary DNA via reverse transcription. Synthesized DNA primers were added to target kallikrein DNA and through PCR, the quantitative level of expression of KLKs 1-15 was recorded. Samples exhibiting high and low KLK expression were selected for immunohistochemistry staining, using a standard protocol.Results from PCR data reveals statistically significant increase in the mean KLK mRNA expression for KLK1, KLK4, KLK10, KLK12 and KLK15 in PLGA tissue samples, as compared with normal salivary gland tissue (Mann Whitney U test, p<0.05).Immunohistochemistry results demonstrate tumour specific staining. Notably, all samples demonstrating relatively higher KLK mRNA expression showed equivalent or increased staining grade scores relative to the low KLK mRNA expression samples, with respect to a specific KLK.In tissue samples of polymorphous low grade adenocarcinoma there is an increase of KLK1, KLK4, KLK10, KLK12 and KLK15 mRNA relative to normal salivary gland tissue. Furthermore, the tumour cells stain positively and specifically for kallikreins.

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Hotspot activating PRKD1 somatic mutations in polymorphous low-grade adenocarcinomas of the salivary glands

Cited by 195 publications

References 55 publications

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Tumors of the Salivary Gland

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Tumors of the Salivary Gland

Giant cribriform adenocarcinoma of the tongue showing PRKD3 rearrangement

Expression of Human Tissue Kallikreins (KLKs) in Polymorphous Low Grade Adenocarcinoma (PLGA)

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