Subsets of salivary duct carcinoma defined by morphologic evidence of pleomorphic adenoma, PLAG1 or HMGA2 rearrangements, and common genetic alterations.

نویسندگان

  • Simion I Chiosea
  • Lester D R Thompson
  • Ilan Weinreb
  • Julie E Bauman
  • Alyssa M Mahaffey
  • Caitlyn Miller
  • Robert L Ferris
  • William E Gooding
چکیده

BACKGROUND The authors hypothesized that histogenetic classification of salivary duct carcinoma (SDC) could account for de novo tumors and those with morphologic or molecular evidence (pleomorphic adenoma gene 1 [PLAG1], high-mobility group AT hook 2 [HMGA2] rearrangement, amplification) of pleomorphic adenoma (PA). METHODS SDCs (n = 66) were reviewed for morphologic evidence of PA. PLAG1 and HMGA2 alterations were detected by fluorescence in situ hybridization (FISH). PLAG1-positive tumors were tested by FISH for fibroblast growth factor receptor 1 (FGFR1) rearrangement. Thirty-nine tumors were analyzed using a commercial panel for mutations and copy number variations in 50 cancer-related genes. RESULTS On the basis of combined morphologic and molecular evidence of PA, 4 subsets of SDC emerged: 1) carcinomas with morphologic evidence of PA but intact PLAG1 and HMGA2 (n = 22); 2) carcinomas with PLAG1 alteration (n = 18) or 3) HMGA2 alteration (n = 12); and 4) de novo carcinomas, without morphologic or molecular evidence of PA (n = 14). The median disease-free survival was 37 months (95% confidence interval, 28.4-45.6 months). Disease-free survival and other clinicopathologic parameters did not differ for the subsets defined above. Combined Harvey rat sarcoma viral oncogene homolog/phosphatidylinositol-4,5-biphosphate 3-kinase, catalytic subunit α (HRAS/PIK3CA) mutations were observed predominantly in de novo carcinomas (5 of 8 vs 2 of 31 tumors; P = .035). Erb-B2 receptor tyrosine kinase 2 (ERBB2) copy number gain was not observed in de novo carcinomas (0 of 8 vs 12 of 31 tumors; P = .08). Tumor protein 53 (TP53) mutations were more common in SDC ex pleomorphic adenomas than in de novo carcinomas (17 of 31 vs 1 of 8 tumors; P = .033). CONCLUSIONS The genetic profile of SDC varies with the absence or presence of pre-existing PA and its cytogenetic signature. Most de novo SDCs harbor combined HRAS/PIK3CA mutations and no ERBB2 amplification. Cancer 2016;122:3136-44. © 2016 American Cancer Society.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Correlated Expression of HMGA2 and PLAG1 in Thyroid Tumors, Uterine Leiomyomas and Experimental Models

In pleomorphic adenomas of the salivary glands (PASG) recurrent chromosomal rearrangements affecting either 8q12 or 12q14∼15 lead to an overexpression of the genes of the genuine transcription factor PLAG1 or the architectural transcription factor HMGA2, respectively. Both genes are also affected by recurrent chromosomal rearrangements in benign adipocytic tumors as e. g. lipomas and lipoblasto...

متن کامل

MDM2 and CDK4 amplifications are rare events in salivary duct carcinomas

Salivary duct carcinoma (SDC) is an aggressive adenocarcinoma of the salivary glands associated with poor clinical outcome. SDCs are known to carry TP53 mutations in about 50%, however, only little is known about alternative pathogenic mechanisms within the p53 regulatory network. Particularly, data on alterations of the oncogenes MDM2 and CDK4 located in the chromosomal region 12q13-15 are lim...

متن کامل

GSK3β and CREB3 Gene Expression Profiling in Benign and Malignant Salivary Gland Tumors

Background: Salivary gland tumors (SGT) are rare lesions with uncertain histopathology. One of the major signaling pathways that participate in the development of several tumors is protein kinase A. In this pathway, glycogen synthase kinase β (GSK3β) and cAMP responsive element binding protein (CREB3) are two genes which are supposed to be down regulated in most human tumors. The expression lev...

متن کامل

An update on salivary gland pathology.

Over the past few decades, salivary gland tumor pathology has evolved. This includes recognition of newly defined entities as well as reclassification of other salivary gland tumors [1]. The development of genetic tests have shown that some salivary gland tumors have genetic abnormalities which are specific to a histologic type such as MECT1– MAML2 gene fusion in mucoepidermoid carcinoma and PL...

متن کامل

Particular aspects in the cytogenetics and molecular biology of salivary gland tumours – current review of reports

Salivary gland tumours are a group of lesions whose heterogeneity of biological and pathological features is widely reflected in the molecular aspect. This is demonstrated by an increasing number of studies in the field of genetics of these tumours. The aim of this study was to collect the most significant scientific reports on the cytogenetic and molecular data concerning these tumours, which ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Cancer

دوره 122 20  شماره 

صفحات  -

تاریخ انتشار 2016