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ABSTRACT Background and Aim Pseudomyxoma peritonei (PMP) is an unusual condition with unique behaviour caused by a mucinous neoplasm, usually arising from the appendix. The aim of this study was to evaluate the prevalence of genomic alterations in clinical specimens of PMP using a targeted assay and correlate the findings with clinical, pathological and outcome data. Sequencing data from 223 patients were analysed. Results The median follow‐up interval was 48 months. The primary neoplasm was appendiceal in 216 patients, ovarian in 4, urachal in 2 and renal in one. We confirmed common mutations in GNAS and KRAS (42% each) with significant co‐occurrence of variants in these genes. TP53 mutations were found in 8%. Other mutations were rare but included novel mutations in BAP1 and ERBB4. Of 17 patients with acellular peritoneal mucin, 6 (35%) were positive for DNA mutations. The non‐appendiceal cases generally showed a similar mutational landscape to the appendiceal lesions with GNAS and KRAS commonly mutated, although one urachal lesion showed multi‐hit TP53 mutation without variants in either GNAS or KRAS. Survival was significantly associated with the grade of the primary neoplasm, the grade of the peritoneal disease, the completeness of cytoreduction score and with mutation in either GNAS, KRAS or both. The hazard ratio (HR) associated with mutation in GNAS and/or KRAS was 1.87 (p = 0.004). Conclusions Survival outcome was more closely associated with the grade of the peritoneal disease than with the grade of the primary neoplasm. Our findings support the developing concept that mutational analysis may provide prognostic information in patients with PMP.

Abstract Background Rhabdomyosarcomas (RMS) are predominantly paediatric sarcomas thought to originate from muscle precursor cells due to impaired myogenic differentiation. Despite intensive treatment, 5-year survival for patients with advanced disease remains low (

Background Diagnostic testing for primary ciliary dyskinesia (PCD) started in 2013 in Palestine. We aimed to describe the diagnostic, genetic and clinical spectrum of the Palestinian PCD population. Methods Individuals with symptoms suggestive of PCD were opportunistically considered for diagnostic testing: nasal nitric oxide (nNO) measurement, transmission electron microscopy (TEM) and/or PCD genetic panel or whole-exome testing. Clinical characteristics of those with a positive diagnosis were collected close to testing including forced expiratory volume in 1 s (FEV1) Global Lung Index z-scores and body mass index z-scores. Results 68 individuals had a definite positive PCD diagnosis, 31 confirmed by genetic and TEM results, 23 by TEM results alone, and 14 by genetic variants alone. 45 individuals from 40 families had 17 clinically actionable variants and four had variants of unknown significance in 14 PCD genes. CCDC39, DNAH11 and DNAAF11 were the most commonly mutated genes. 100% of variants were homozygous. Patients had a median age of 10.0 years at diagnosis, were highly consanguineous (93%) and 100% were of Arabic descent. Clinical features included persistent wet cough (99%), neonatal respiratory distress (84%) and situs inversus (43%). Lung function at diagnosis was already impaired (FEV1 z-score median −1.90 (−5.0–1.32)) and growth was mostly within the normal range (z-score mean −0.36 (−3.03–2.57). 19% individuals had finger clubbing. Conclusions Despite limited local resources in Palestine, detailed geno- and phenotyping forms the basis of one of the largest national PCD populations globally. There was notable familial homozygosity within the context of significant population heterogeneity.