Integrative Molecular and Clinical Profiling of Acral Melanoma Identifies LZTR1 as a Key Tumor Promoter and Therapeutic Target

Acral melanoma, the most common melanoma subtype among non-Caucasian individuals, is associated with poor prognosis. However, its key molecular drivers remain obscure. Here, we performed integrative genomic and clinical profiling of acral melanomas from a cohort of 104 patients treated in North America or China. We found that recurrent, late-arising amplifications of cytoband chr22q11.21 are a leading determinant of inferior survival, strongly associated with metastasis, and linked to downregulation of immunomodulatory genes associated with response to immune checkpoint blockade. Unexpectedly, LZTR1 – a known tumor suppressor in other cancers – is a key candidate oncogene in this cytoband. Silencing of LZTR1 in melanoma cell lines caused apoptotic cell death independent of major hotspot mutations or melanoma subtypes. Conversely, overexpression of LZTR1 in normal human melanocytes initiated processes associated with metastasis, including anchorage-independent growth, formation of spheroids, and increased levels of MAPK and SRC activities. Our results provide new insights into the etiology of acral melanoma and implicate LZTR1 as a key tumor promoter and therapeutic target

Integrative molecular and clinical profiling of acral melanoma identifies LZTR1 as a key tumor promoter and therapeutic target

Acral melanoma, the most common melanoma subtype among non-Caucasian individuals, is associated with poor prognosis. However, its key molecular drivers remain obscure. Here, we performed integrative genomic and clinical profiling of acral melanomas from a cohort of 104 patients treated in North America or China. We found that recurrent, late-arising amplifications of cytoband chr22q11.21 are a leading determinant of inferior survival, strongly associated with metastasis, and linked to downregulation of immunomodulatory genes associated with response to immune checkpoint blockade. Unexpectedly, LZTR1 - a known tumor suppressor in other cancers - is a key candidate oncogene in this cytoband. Silencing of LZTR1 in melanoma cell lines caused apoptotic cell death independent of major hotspot mutations or melanoma subtypes. Conversely, overexpression of LZTR1 in normal human melanocytes initiated processes associated with metastasis, including anchorage-independent growth, formation of spheroids, and increased levels of MAPK and SRC activities. Our results provide new insights into the etiology of acral melanoma and implicate LZTR1 as a key tumor promoter and therapeutic target.

Clinical Profiling of a Bilingual Client with Anomic Aphasia

Background: Aphasia is an acquired condition affecting auditory comprehension, verbal expression, reading, writing and word-finding abilities along with sensory-motor impairments. Anomia refers to difficulty in word retrieval or naming which is seen irrespective of the type of aphasia. However, if a patient shows word-finding difficulty, in specific, a diagnosis of Anomic aphasia is made. There are variations within anomic aphasia on which the management and recovery depend. The article provides one such case report. Purpose: Speech and language profiling in anomic aphasia, specific treatment strategies, the effect of bilingualism on recovery. Methods: Mr S, a 38-year-old bilingual male reported 5 months post-stroke with difficulty in expressing, difficulty in writing and weakness in the right side of the body. Medical history was checked and speech and language evaluations including both formal and informal assessments were performed. After this, a diagnosis of Anomic aphasia with mild dysarthria was made. An appropriate speech–language therapeutic plan and specific activities were formulated for Mr S in his first language (L1) and he was given a therapy for a span of 3 months. A follow-up evaluation in both first and second language of the patient yielded differential recovery patterns. Results: The diagnosis was affected by different variants of anomic aphasia; treatment was specific to the clinical profiling and followed life-participation approach of aphasia. The recovery was affected by differential recovery patterns between the languages. Discussion: Factors pertaining to diagnosis, recovery, bilingualism and treatment of the client with anomic aphasia are discussed.

Clinical profiling of subclinical hypothyroidism at presentation at tertiary care center

Background: Subclinical hypothyroidism (SCH) is defined as serum thyroid-stimulating hormone (TSH) level above upper limit of normal despite normal levels of serum free thyroxine, stable over a period of one month in the absence of any non thyroidal illness. Present study is aimed at evaluating prevalence of SCH in developing countries and evaluating the clinical spectrum of these patients highlighting the importance of treatment of SCH.Methods: Total number of 120 patients with established SCH was enrolled for the study over 3 years. The values were measured by third generation non-isotopic immunochemiluminiscence method using the standard protocol as indicated in the kit.Results: Patients were aged 15-50 years old. The most common manifestation was generalized weakness, lethargy and tiredness (60%) followed by generalized body ache (52.5%). 46.7% % of the patients had complaints of weight gain. Triglyceride levels and serum cholesterol levels were deranged in 28.3% of all cases. Body mass index was increased in 28.3% of all patients with obesity in only 2 patients. 15 patients (11.7%) were found to be anaemic with increased MCV and MCH/MCHC, attributable to hypothyroidism.Conclusions: These symptoms caused significant debilitated life style and poor outcome in SCH patients. Treatment of these patients can help in improving their lifestyle and perform better on daily basis.