Sterile alpha motif domain protein 9 (SAMD9) and its paralogue SAMD9-like (SAMD9L) are cytoplasmic proteins encoded by two juxtaposed single-exon genes on chromosome 7q21. They share a 60% amino acid sequence identity and likely originated from a duplication of a common ancestral gene 1 . Their function remains enigmatic; they have been linked to tumor suppression 2 , inflammation 3 , stress response 4 , development 4 , endosomal fusion 5,6 and protein translation 7,8 . Both proteins were also shown to function as restriction factors forming a cross-species barrier for poxvirus infection [9][10][11][12] . Structural analysis of these large proteins has been limited to homology modeling, which predicted identical domains in either protein (SAM, ALBA2, SIR2, P-loop/ NTPase and OB-fold) 13 . Moreover, these genes exhibit tight regulation during embryonic development and transition to ubiquitous expression levels in adult tissues 14,15 .Notably, Samd9l-haploinsufficient mice develop myeloid neoplasia mimicking human MDS with monosomy 7 5 . Several groups reported germline SAMD9 or SAMD9L mutations (SAMD9/9L mut ) underlying new human syndromes with a propensity for cytopenia, bone marrow failure (BMF) and MDS with non-random monosomy 7 or deletion of 7q 6,16-28 . SAMD9 mutations (SAMD9 mut ) were initially linked to a fatal, early-onset MIRAGE syndrome (myelodysplasia, infections, restriction of growth, adrenal hypoplasia, genital phenotypes and enteropathy) 6,29 . In contrast, SAMD9L mutations (SAMD9L mut ) were originally described in families with a progressive neurological phenotype, multi-lineage cytopenia and bone marrow hypoplasia (ataxia-pancytopenia syndrome) 16,17 . Recent reports broadened this spectrum and found missense SAMD9/9L mut in non-syndromic familial MDS [30][31][32][33] , truncating SAMD9L mut in children with autoinflammatory panniculitis resembling CANDLE

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The histological subtype is crucial for decisions regarding neck dissection. New molecular parameters may also indicate elective treatment of the neck.

Hepatocyte growth factor receptor (MET) is a key driver of oncogenic transformation. Copy number gain and amplification of MET positively enhance tumour growth, invasiveness and metastasis in different cancer types. In the present study, 266 carcinomas of the major and minor salivary glands were investigated for genomic MET status by fluorescence in situ hybridization and for protein expression by immunohistochemistry. Results were matched with clinicopathological parameters, long-term survival and the status of epidermal growth factor receptor (EGFR) and phosphatase and tensin homologue (PTEN). Low polysomy (n = 42), high polysomy (n = 27), amplification (n = 2) and deletion (n = 18) were found as aberrations of genomic MET in certain subtypes. MET aberrations were associated with increased patient age (>70 years, p = 0.003), male gender (p = 0.01), increased tumour size (p = 0.002), lymph node metastases (p < 0.001), high-grade malignancy (p < 0.001) and unfavourable overall survival (p < 0.001). Both copy number gain (p < 0.001) and deletion (p = 0.031) of MET correlated with copy number gain of EGFR. Tumours with genomic loss of PTEN (n = 48) concurrently presented aberration of genomic MET (p < 0.001). MET gene status significantly correlated with protein status (p = 0.038). In conclusion, gain but also loss of genomic MET activity correlates with aggressive tumour growth, nodal metastasis and worse overall survival in salivary gland cancer. Moreover, aberrations of MET are associated with EGFR and PTEN signalling and might possess relevance for targeted therapies of salivary gland carcinomas in the future.