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Primary lung cancer is rare in dogs and depending on the tumour stage and subtype, the prognosis can be poor. In this report, we describe a 10 year-old female intact Yorkshire terrier that presented progressive weight loss and chronic pain of unknown origin. Due to the poor condition of the dog, it was subsequently euthanized. Post-mortem evaluation revealed a single large mass in the left caudal lung lobe, with numerous pale, proliferative lesions of various sizes dispersed throughout all the lobes. Additionally, a solitary skin mass was palpated on the mid-thoracic body wall. Histopathological examination of the lung samples revealed multiple distinct, non-encapsulated, expansive neoplastic epithelial cell proliferations with dense cellularity, exhibiting growth patterns, ranging from papillary to micropapillary to solid, accompanied by central areas of necrosis. In some areas, microvilli-like structures were observed on the luminal cytoplasmic margins of the neoplastic cells. The histopathology of the skin mass closely resembled that of the lung. Electron microscopy of the skin samples revealed regions containing cells resembling the respiratory epithelium, along with cells exhibiting processes or microvilli indicative of cilia. The diagnosis was pulmonary adenocarcinoma with cutaneous metastasis. This is the first report of a canine with primary lung cancer that metastasized to the skin.
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Molecular biomarkers are central to personalised medicine for human cancer patients. It is gaining traction as part of standard veterinary clinical practice for dogs and cats with cancer. Molecular biomarkers can be somatic or germline genomic alterations and can be ascertained from tissues or body fluids using various techniques. This review discusses how these genomic alterations can be determined and the findings used in clinical settings as diagnostic, prognostic, predictive, and screening biomarkers. We showcase the somatic and germline genomic alterations currently available to date for testing dogs and cats in a clinical setting, discussing their utility in each biomarker class. We also look at some emerging molecular biomarkers that are promising for clinical use. Finally, we discuss the hurdles that need to be overcome in going 'bench to bedside', i.e., the translation from discovery of genomic alterations to adoption by veterinary clinicians. As we understand more of the genomics underlying canine and feline tumours, molecular biomarkers will undoubtedly become a mainstay in delivering precision veterinary care to dogs and cats with cancer.
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Genetic molecular testing is starting to gain traction as part of standard clinical practice for dogs with cancer due to its multi-faceted benefits, such as potentially being able to provide diagnostic, prognostic and/or therapeutic information. However, the benefits and ultimate success of genomic analysis in the clinical setting are reliant on the robustness of the tools used to generate the results, which continually expand as new technologies are developed. To this end, we review the different materials from which tumour cells, DNA, RNA and the relevant proteins can be isolated and what methods are available for interrogating their molecular profile, including analysis of the genetic alterations (both somatic and germline), transcriptional changes and epigenetic modifications (including DNA methylation/acetylation and microRNAs). We also look to the future and the tools that are currently being developed, such as using artificial intelligence (AI) to identify genetic mutations from histomorphological criteria. In summary, we find that the molecular genetic characterisation of canine neoplasms has made a promising start. As we understand more of the genetics underlying these tumours and more targeted therapies become available, it will no doubt become a mainstay in the delivery of precision veterinary care to dogs with cancer.
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Despite their relatively long life-spans, reports of neoplasia in bats are rare and are limited to a handful of cases. In this report, we describe a 2-year-old female wild Cape serotine bat (Laephotis capensis) that had been caught by a domestic cat and presented with a skin mass over the chest area. Histopathological analysis of a subsequent biopsy revealed proliferating sheets of neoplastic round cells, occasionally appearing to form packets, supported by a fine, fibrovascular stroma. Marked nuclear pleomorphism was seen, as well as a high mitotic count. Immunohistochemistry displayed positive labelling for MUM1 in the neoplastic cells. The diagnosis was extramedullary plasmacytoma (EMP); a neoplasm consisting of plasma cells derived from B lymphocytes. Due to a deteriorating condition, the bat was anaesthetised, and the mass was surgically removed two weeks later. However, the bat succumbed under the anaesthetic. Histopathological examination of the mass showed the same neoplastic cell population as observed in the biopsy; in addition, there was a locally extensive infiltration of neoplastic cells in the spleen and a mild presence of neoplastic cells in circulation. This is the first report of an EMP in a bat, and we compare the findings with that seen in dogs and cats.
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In dogs, the BRAF mutation (V595E) is common in bladder and prostate cancer and represents a specific diagnostic marker. Recent advantages in artificial intelligence (AI) offer new opportunities in the field of tumour marker detection. While AI histology studies have been conducted in humans to detect BRAF mutation in cancer, comparable studies in animals are lacking. In this study, we used commercially available AI histology software to predict BRAF mutation in whole slide images (WSI) of bladder urothelial carcinomas (UC) stained with haematoxylin and eosin (HE), based on a training (n = 81) and a validation set (n = 96). Among 96 WSI, 57 showed identical PCR and AI-based BRAF predictions, resulting in a sensitivity of 58% and a specificity of 63%. The sensitivity increased substantially to 89% when excluding small or poor-quality tissue sections. Test reliability depended on tumour differentiation (p < 0.01), presence of inflammation (p < 0.01), slide quality (p < 0.02) and sample size (p < 0.02). Based on a small subset of cases with available adjacent non-neoplastic urothelium, AI was able to distinguish malignant from benign epithelium. This is the first study to demonstrate the use of AI histology to predict BRAF mutation status in canine UC. Despite certain limitations, the results highlight the potential of AI in predicting molecular alterations in routine tissue sections.
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Cancer is a significant cause of morbidity and mortality in felines, with the majority of tumours (53-85% cases) being diagnosed as malignant [...].
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Melanoma is a tumour that arises from the uncontrolled proliferation of melanocytes (pigment-producing cells) found in the skin (cutaneous melanoma and digital melanoma), mucosal surfaces (oral melanoma), and the eye (ocular melanoma) [...].
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Schwannoma is a nerve sheath tumour arising from differentiated Schwann cells, and melanocytic schwannoma (MS) is a rare variant where the Schwan cells produce melanin pigment. MS is typically associated with spinal nerve roots and there have been only ~20 reports of cutaneous or subcutaneous MS to-date in humans. In canines, there have only been two reports of MS, both associated with spinal root nerves. In this report, we describe a 7-year-old Weimaraner cross breed dog that presented with two pigmented lesions on the eyelids. The lesions were surgically removed and histological analysis revealed well-circumscribed, non-encapsulated, expansile, neoplasms that were displacing most of the dermis and adnexa. The first lesion was composed of spindloid cells arranged in short interlacing streams with large amounts of pale eosinophilic cytoplasm that sometimes contained fine melanin granules. In areas there were spindle cells arranged in verocay bodies which led to a diagnosis of MS. In contrast, the second lesion was composed of polygonal cells arranged in thick sheets with large amounts of pale eosinophilic cytoplasm that sometimes contained fine melanin granules. The diagnosis was melanocytoma (which is one of the macroscopic differential diagnoses for MS). Whilst melanocytoma is a commonly occurring cutaneous lesion in canines and surgical removal is considered curative, due to little being known about MS in dogs, the outcome remained guarded, as MS in humans has an unpredictable nature, and recurrence and metastasis have been reported.
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Cancer is a significant cause of morbidity and mortality in domestic cats. In humans, an understanding of the oncogenome of different cancer types has proven critical and is deeply interwoven into all aspects of patient care, including diagnostics, prognostics and treatments through the application of targeted therapies. Investigations into understanding the genetics of feline cancers started with cytogenetics and was then expanded to studies at a gene-specific level, looking for mutations and expression level changes of genes that are commonly mutated in human cancers. Methylation studies have also been performed and together with a recently generated high-quality reference genome for cats, next-generation sequencing studies are starting to deliver results. This review summarises what is currently known of the genetics of both common and rare cancer types in cats, including lymphomas, mammary tumours, squamous cell carcinomas, soft tissue tumours, mast cell tumours, haemangiosarcomas, pulmonary carcinomas, pancreatic carcinomas and osteosarcomas. Shining a spotlight on our current understanding of the feline oncogenome will hopefully serve as a springboard for more much-needed research into the genetics of cancer in domestic cats.
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Meningiomas are the most common primary brain tumour in dogs and cats. However, whilst there are numerous reports of extracranial (spinal, orbital and sinonasal) meningiomas in the dog, there have only been a few case reports of spinal meningiomas, and no post-mortem confirmed orbital or sinonasal meningiomas in cats. In this report, a 20-year-old captive tiger (Panthera tigris altaica) with a history of chronic ocular inflammation resulting in enucleation, spontaneously developed tetanic convulsions (epileptic seizures) that over a 2-year period resulted in a gradually worsening condition and the animal was eventually euthanized. At autopsy, a focal, expansile, neoplastic mass was found in the caudal nasal cavity midline, abutting the cribriform plate and slightly compressing the calvarium. Histological analysis revealed nasal turbinates attached to a well-circumscribed expansile multi-lobular mass consisting of interlacing whorls and streams of neoplastic cells supported by a variably fibrous to microcystic collagenous matrix displaying rare psammoma bodies. The diagnosis was sinonasal transitional meningioma. This is the first report of a captive wild felid with an extracranial meningioma, specifically a tiger with a sinonasal transitional meningioma.
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Mutationally activated BRAF is detected in approximately 7% of human lung adenocarcinomas, with BRAFT1799A serving as a predictive biomarker for treatment of patients with FDA-approved inhibitors of BRAFV600E oncoprotein signaling. In genetically engineered mouse (GEM) models, expression of BRAFV600E in the lung epithelium initiates growth of benign lung tumors that, without additional genetic alterations, rarely progress to malignant lung adenocarcinoma. To identify genes that cooperate with BRAFV600E for malignant progression, we used Sleeping Beauty-mediated transposon mutagenesis, which dramatically accelerated the emergence of lethal lung cancers. Among the genes identified was Rbms3, which encodes an RNA-binding protein previously implicated as a putative tumor suppressor. Silencing of RBMS3 via CRISPR/Cas9 gene editing promoted growth of BRAFV600E lung organoids and promoted development of malignant lung cancers with a distinct micropapillary architecture in BRAFV600E and EGFRL858R GEM models. BRAFV600E/RBMS3Null lung tumors displayed elevated expression of Ctnnb1, Ccnd1, Axin2, Lgr5, and c-Myc mRNAs, suggesting that RBMS3 silencing elevates signaling through the WNT/ß-catenin signaling axis. Although RBMS3 silencing rendered BRAFV600E-driven lung tumors resistant to the effects of dabrafenib plus trametinib, the tumors were sensitive to inhibition of porcupine, an acyltransferase of WNT ligands necessary for their secretion. Analysis of The Cancer Genome Atlas patient samples revealed that chromosome 3p24, which encompasses RBMS3, is frequently lost in non-small cell lung cancer and correlates with poor prognosis. Collectively, these data reveal the role of RBMS3 as a lung cancer suppressor and suggest that RBMS3 silencing may contribute to malignant NSCLC progression. SIGNIFICANCE: Loss of RBMS3 cooperates with BRAFV600E to induce lung tumorigenesis, providing a deeper understanding of the molecular mechanisms underlying mutant BRAF-driven lung cancer and potential strategies to more effectively target this disease.
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Adenocarcinoma del Pulmón , Carcinogénesis , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Proteínas Proto-Oncogénicas B-raf , Proteínas de Unión al ARN , Transactivadores , Animales , Humanos , Ratones , Adenocarcinoma del Pulmón/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Proliferación Celular , Pulmón/patología , Neoplasias Pulmonares/genética , Mutagénesis , Proteínas Proto-Oncogénicas B-raf/metabolismo , Proteínas de Unión al ARN/genética , Transactivadores/metabolismo , Vía de Señalización Wnt , Carcinogénesis/genéticaRESUMEN
A nine-year-old intact female sable antelope (Hippotragus niger) with a six-week history of gradual loss of body condition was found dead by the owner and presented for autopsy. Macroscopic examination revealed an enlarged spleen and liver with the hepatic and splenic parenchyma showing extensive infiltration with firm, white to cream-coloured nodules. The uterus showed a few small, firm, well-demarcated, white-to-cream-coloured nodules in the uterine body. Similar nodules were present in the mediastinum, parietal pleura, heart, and marrow cavity of the femur. Histological analysis of the uterus revealed densely cellular neoplastic proliferations, forming nests, tubules, and acini within an abundant fibrovascular stroma. The samples from the other tissues revealed neoplastic cells with a similar appearance to those seen in the uterus, also forming nests and acini in a fibrovascular stroma. Importantly, multiple neoplastic cells were also seen in the peribronchiolar lymphatic vessels. The neoplastic cells in the uterine sections showed positive immunohistochemical labelling for cytokeratin, as did the neoplastic cells in the sections of liver and parietal pleura, confirming they were of epithelial origin. In addition, transmission electron microscopy of the uterus and liver showed neoplastic cells arranged in groups surrounded by basement membranes and interspersed with collagen fibres. Junctions were present between the cells, and junctional complexes could be seen at some cell surfaces. This confirmed that the neoplastic cells seen in the liver sample were the same as those seen in the uterine sample and were of epithelial origin. Thus, a diagnosis was made of uterine adenocarcinoma with widespread metastasis. This is the first report of uterine adenocarcinoma in a sable antelope.
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A 15-year-old spayed female Sumatran tiger (Panthera tigris sondaica) was presented with a short history of haematuria and dysuria, non-responsive to antibiotics, and a gradual decline to inappetence over a period of 2-3 months. Ultrasound examination showed a thickened urinary bladder wall and the renal pelvis of right kidney was dilated and cystic. A presumptive diagnosis of renal failure was made, and the tigress was euthanised due to deteriorating quality of life and pronounced weight loss. Histopathology revealed extensive erosion of the urinary bladder wall and marked congestion of the submucosal vasculature, a potential cause of the haematuria observed clinically. Numerous foci of neoplastic cells were also observed throughout the lung parenchyma as well as within lymphatic vessels of the lung, the liver and the kidney. A diagnosis of a metastatic non-papillary high-grade urothelial carcinoma (UC) of the urinary bladder was made. Consistent with this diagnosis, immunohistochemistry revealed the neoplastic cells were negative for uroplakin III, as has been reported for a subset of high-grade, infiltrative urinary bladder UCs of canines and humans. This is the first report of a primary tumour of the urinary bladder in a tiger and the first report of UC in a tiger.
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Carcinoma de Células Transicionales , Enfermedades de los Perros , Tigres , Neoplasias de la Vejiga Urinaria , Animales , Carcinoma de Células Transicionales/veterinaria , Perros , Femenino , Hematuria/veterinaria , Calidad de Vida , Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/veterinariaRESUMEN
Primary cutaneous and mucosal melanoma shows a wide histological spectrum. The correct diagnosis depends upon the demonstration of melanocytic differentiation by recognition of an associated in-situ component or immunohistochemical evidence of a melanocytic phenotype using conventional melanocytic markers, such as S-100, SOX10, Melan-A and HMB-45. Exceptionally, melanomas lose their melanocytic phenotype, at least focally, and show differentiation towards other lineages. Review of the literature shows that de- and trans-differentiation in melanoma is rare but probably under-recognised and under-reported. These often large and frequently ulcerated tumours affect adults and show a wide anatomical distribution, including mucosal sites, although there is a predilection for sun-damaged skin of the head and neck. Histologically, the tumours are biphasic and contain a pre-existing conventional melanoma. The de-differentiated component closely resembles atypical fibroxanthoma, both morphologically and immunohistochemically. Trans-differentiated melanoma may show rhabdomyosarcomatous or spindle cell carcinomatous features. Undifferentiated melanomas are similar tumours in which the conventional melanoma component is absent. Their diagnosis depends entirely upon the clinical context and identification of a classical melanoma driver gene mutation, i.e. BRAF V600E. The diagnosis of these rare and unusual tumours is challenging, and requires thorough tumour sampling and recognition of the background of a pre-existing but often focal conventional melanoma together with molecular analysis.
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Desdiferenciación Celular/fisiología , Diferenciación Celular/fisiología , Melanoma/patología , Neoplasias Cutáneas/patología , Piel/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Humanos , Melanoma/genética , Melanoma/metabolismo , Mutación , Piel/metabolismo , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/metabolismoRESUMEN
Reptiles are popular exotic pets and green iguanas (Iguana iguana) are amongst the top ten most popular reptiles. Here we describe a captive 8-year-old female green iguana that was referred for treatment of a non-healing, discharging lesion on the side of the body. The lesion was surgically excised and histopathological analysis revealed an epidermal proliferation of neoplastic keratinocytes, with focal infiltration through the basement membrane, into the underlying superficial dermis. Marked dysplastic changes, characterized by multifocal dyskeratosis and keratin pearl formation were also noted. A diagnosis of cutaneous squamous cell carcinoma (SCC) was made. Two years later, the iguana has shown no signs of recurrence. This is the first report of successful treatment of cutaneous SCC in a green iguana and contributes to the limited knowledge of cutaneous neoplasms in green iguanas.
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Carcinoma de Células Escamosas , Iguanas , Neoplasias Cutáneas , Animales , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/veterinaria , Femenino , Neoplasias Cutáneas/cirugía , Neoplasias Cutáneas/veterinariaRESUMEN
Malignant melanomas tend to be locally destructive, aggressive tumours commonly associated with recurrence and/or metastasis. In this report, a 13-year-old captive white African lioness (Panthera leo), with a recent history of intermittent bouts of lethargy and inappetence, presented with a distended abdomen (due to ascites) and a small, round crusty lesion on the ear. An abdominal ultrasound showed the presence of masses on the liver and an exploratory laparotomy revealed multiple pale lesions on the liver and omentum. Histopathology revealed sheets of pleomorphic neoplastic cells compressing the non-neoplastic liver tissue. Similar neoplastic cells had multifocally expanded and effaced omentum adipose tissue, as well as formed a well-circumscribed mass in the ear sample, extending from close to the epidermis to the lateral and deep margins of the section. All three tissue samples had a high mitotic index (15 per 10 HPF), and critically, in the ear sample, there were rafts of neoplastic cells in the lymphatics, indicating lymphovascular invasion. Immunohistochemistry for the melanoma marker, PNL-2, showed strong positivity in all three tissue samples. Thus, the diagnosis was of malignant melanoma with metastasis to the liver and omentum. This is the first report of metastatic cutaneous melanoma in a lion.
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Angiosarcoma (AS) is a highly aggressive tumor of blood and lymphatic vessels in humans that shares many similarities with spontaneously occurring hemangiosarcoma (HSA) in dogs and cats. To investigate the genetic suitability of HSA as a model for AS, we sequenced â¼1000 cancer genes in 41 cases of HSA and matched germline tissue: 15 canine visceral HSAs, 13 canine skin HSAs and 13 feline skin HSAs. Analysis of visceral HSAs from dogs presenting with concurrent splenic and cardiac neoplasms showed that the tumors were not independent primaries, consistent with the highly metastatic nature of HSA. Comparison of HSA to AS revealed that several driver genes were recurrently mutated in both species, such as TP53, PIK3CA, ATRX, GRIN2A and LRP1B. Similar to AS, a UV mutational signature was found in a subset of canine cutaneous HSAs and both species show differing mutational profiles between tissue sites. Our characterization of canine and feline HSA demonstrates many important parallels to AS and provides hope that future studies on these cancers will benefit of all three species.
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Enfermedades de los Gatos , Enfermedades de los Perros , Hemangiosarcoma , Animales , Enfermedades de los Gatos/genética , Gatos , Enfermedades de los Perros/genética , Enfermedades de los Perros/patología , Perros , Hemangiosarcoma/genética , Hemangiosarcoma/patología , Hemangiosarcoma/veterinaria , Humanos , Mutación/genética , OncogenesRESUMEN
Cutaneous squamous cell carcinoma (SCC) is a slow growing but locally invasive neoplasm, most commonly caused by prolonged exposure to ultraviolet (UV) radiation. Whilst SCC accounts for 15% of skin tumours in domesticated cats, cutaneous SCC in non-domesticated felids (apart from captive snow leopards) appears to be uncommon, with only three reports in the literature to date. In this report, a captive African lion (Panthera leo) presented with two ulcerative lesions on the nasal planum. Histopathology of the lesions revealed epidermal keratinocyte dysplasia and neoplastic basal- and supra-basal epithelial cells with dyskeratosis and evidence of basement membrane breaching and dermal invasion, consistent with a diagnosis of SCC. There was also evidence of laminar fibrosis and inflammation of the subjacent dermis suggesting that the SCC most likely resulted from UV-induced neoplastic transformation of the epidermal squamous epithelium following actinic keratosis. The lion was treated with hypofractionated radiation therapy and remained in remission until his death (euthanised 17 months later because of age-related chronic renal failure). This is the first report of cutaneous SCC in a lion with evidence of actinic damage and resolution after radiation therapy.
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Carcinoma de Células Escamosas/veterinaria , Leones , Neoplasias Nasales/veterinaria , Hipofraccionamiento de la Dosis de Radiación , Neoplasias Cutáneas/veterinaria , Animales , Carcinoma de Células Escamosas/radioterapia , Masculino , Neoplasias Nasales/radioterapia , Neoplasias Cutáneas/radioterapiaRESUMEN
Dedifferentiation and transdifferentiation are rare and only poorly understood phenomena in cutaneous melanoma. To study this disease more comprehensively we have retrieved 11 primary cutaneous melanomas from our pathology archives showing biphasic features characterized by a conventional melanoma and additional areas of de-/trans-differentiation as defined by a lack of immunohistochemical expression of all conventional melanocytic markers (S-100 protein, SOX10, Melan-A, and HMB-45). The clinical, histologic, and immunohistochemical findings were recorded and follow-up was obtained. The patients were mostly elderly (median: 81 years; range: 42-86 years) without significant gender predilection, and the sun-exposed skin of the head and neck area was most commonly affected. The tumors were deeply invasive with a mean depth of 7 mm (range: 4-80 mm). The dedifferentiated component showed atypical fibroxanthoma-like features in the majority of cases (7), while additional rhabdomyosarcomatous and epithelial transdifferentiation was noted histologically and/or immunohistochemically in two tumors each. The background conventional melanoma component was of desmoplastic (4), superficial spreading (3), nodular (2), lentigo maligna (1), or spindle cell (1) types. For the seven patients with available follow-up data (median follow-up period of 25 months; range: 8-36 months), two died from their disease, and three developed metastases. Next-generation sequencing of the cohort revealed somatic mutations of established melanoma drivers including mainly NF1 mutations (5) in the conventional component, which was also detected in the corresponding de-/trans-differentiated component. In summary, the diagnosis of primary cutaneous de-/trans-differentiated melanoma is challenging and depends on the morphologic identification of conventional melanoma. Molecular analysis is diagnostically helpful as the mutated gene profile is shared between the conventional and de-/trans-differentiated components. Importantly, de-/trans-differentiation does not appear to confer a more aggressive behavior.
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Genómica , Melanoma/patología , Neurofibromina 1/genética , Neoplasias Cutáneas/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Diferenciación Celular , ADN de Neoplasias/genética , Diagnóstico Diferencial , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Melanoma/genética , Melanoma/metabolismo , Persona de Mediana Edad , Proteínas de Neoplasias/metabolismo , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/metabolismoRESUMEN
Metastasis is the spread of cancer cells to a secondary site within the body, and is the leading cause of death for cancer patients. The lung is a common site of metastasis for many cancer types, including melanoma. Identifying the genes involved in aiding metastasis of melanoma cells to the lungs is critical for the development of better treatments. As the accessibility of cell surface proteins makes them attractive therapeutic targets, we performed a CRISPR activation screen using a library of guide RNAs (gRNAs) targeting the transcription start sites of 2195 membrane protein-encoding genes, to identify genes whose upregulated expression aided pulmonary metastasis. Immunodeficient mice were subcutaneously injected in the flank with murine B16-F0 melanoma cells expressing dCas9 and the membrane protein library gRNAs, and their lungs collected after 14-21 days. Analysis was performed to identify the gRNAs that were enriched in the lungs relative to those present in the cells at the time of administration (day 0). We identified six genes whose increased expression promotes lung metastasis. These genes included several with well-characterized pro-metastatic roles (Fut7, Mgat5, and Pcdh7) that have not previously been linked to melanoma progression, genes linked to tumor progression but that have not previously been described as involved in metastasis (Olfr322 and Olfr441), as well as novel genes (Tmem116). Thus, we have identified genes that, when upregulated in melanoma cells, can aid successful metastasis and colonization of the lung, and therefore may represent novel therapeutic targets to inhibit pulmonary metastasis.