KRAS, NRAS and BRAF Mutational Profile of Colorectal Cancer in a Series of Moroccan Patients.

OBJECTIVES: The present study aimed to evaluate the frequencies of KRAS, NRAS, and BRAF mutations and their possible associations with clinicopathological features in 249 Moroccan patients with colorectal cancer (CRC). METHODS: A retrospective investigation of a cohort of formalin-fixed paraffin-embedded tissues of 249 patients with CRC was screened for KRAS/NRAS/BRAF mutations using Idylla™ technology and pyrosequencing. RESULTS: KRAS, NRAS, and BRAF mutations were revealed in 46.6% (116/249), 5.6% (14/249), and 2.4% (6/249) of patients. KRAS exon 2 mutations were identified in 87.9% of patients (102/116). KRAS G12D and G12 C were the most frequent, at 32.8% and 12.93%, respectively. Among the patients with KRAS exon 2 wild-type (wt), 27.6% (32/116) harbored additional KRAS mutations. Concurrent KRAS mutations were identified in 9.5% (11/116); including six in codon 146 (A146P/T/V), three in codon 61 (Q61H/L/R), one in codon 12 (G12 A and Q61H), and one in codon 13 (G13D and Q61 L). Among the NRAS exon 2 wt patients, 64.3% (9/14) harbored additional NRAS mutations. Concurrent NRAS mutations were identified in 28.6% (4/14) of NRAS-mutant patients. Since 3.2% wt KRAS were identified with NRAS mutations, concomitant KRAS and NRAS mutations were identified in 2.4% (6/249) of patients. KRAS mutations were higher in the >50-year-old age-group (P = .031), and the tumor location was revealed to be significantly associated with KRAS mutations (P = .028) predominantly in left colon (27.5%) and colon (42.2%) locations. NRAS mutations were most prevalent in the left colon (42.8%) and in well-differentiated tumors (64.2%). CONCLUSION: Detection of KRAS mutations, particularly the G12 C subtype, may be significant for patients with CRC and has possible therapeutic implications. However, rare KRAS concomitant mutations in CRC patients suggest that each individual may present distinct therapeutic responses. KRAS testing alongside the identification of other affected genes in the same patient will make the treatments even more personalized by contributing more accurately to the clinical decision process. Overall, early diagnosis using novel molecular techniques may improve the management of CRC by providing the most efficient therapies for Moroccan patients.

Prevalence and patterns of mutations in RAS/RAF/MEK/ERK/MAPK signaling pathway in colorectal cancer in North Africa.

BACKGROUND: Our review discuss (i) the findings from analyzed data that have examined KRAS, NRAS and BRAF mutations in patients with colorectal cancer (CRC) in North Africa and to compare its prevalence with that shown in other populations and (ii) the possible role of dietary and lifestyle factors with CRC risk.  METHODS: Using electronic databases, a systematic literature search was performed for the KRAS, NRAS, and BRAF mutations in CRC patients from Morocco, Tunisia, Algeria and Lybia.  RESULTS: Seventeen studies were identified through electronic searches with six studies conducted in Morocco, eight in Tunisia, two in Algeria, and one in Libya. A total of 1843 CRC patients were included 576 (31.3%) in Morocco, 641 (34.8%) in Tunisia, 592 (32.1%) in Algeria, and 34 (1.8%) in Libya. Overall, the average age of patients was 52.7 years old. Patients were predominantly male (56.6%). The mutation rates of KRAS, NRAS and BRAF were 46.4%, 3.2% and 3.5% of all patients, respectively. A broad range of reported KRAS mutation frequencies have been reported in North Africa countries. The KRAS mutation frequency was 23.9% to 51% in Morocco, 23.1% to 68.2% in Tunisia, 31.4% to 50% in Algeria, and 38.2% in Libya. The G12D was the most frequently identified KRAS exon 2 mutations (31.6%), followed by G12V (25.4%), G13D (15.5%), G12C (10.2%), G12A (6.9%), and G12S (6.4%). G12R, G13V, G13C and G13R are less than 5%. There are important differences among North Africa countries. In Morocco and Tunisia, there is a higher prevalence of G12D mutation in KRAS exon 2 (≈50%). The most frequently mutation type in KRAS exon 3 was Q61L (40%). A59T and Q61E mutations were also found. In KRAS exon 4, the most common mutation was A146T (50%), followed by K117N (33.3%), A146P (8.3%) and A146V (8.3%). CONCLUSION: KRAS mutated CRC patients in North Africa have been identified with incidence closer to the European figures. Beside established anti-CRC treatment, better understanding of the causality of CRC can be established by combining epidemiology and genetic/epigenetic on CRC etiology. This approach may be able to significantly reduce the burden of CRC in North Africa.

Reactivation of cytomegalovirus in a patient with stevens-johnson syndrome-toxic epidermal necrolysis.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe adverse cutaneous reactions to drugs. We describe the case of a 19 year old patient with SJS/TEN overlap syndrome, who developed severe interstitial pneumonia after she had received antiepileptic drugs. A cytomegalovirus infection was diagnosed by Real Time Polymerase Chain Reaction (RT-PCR) detection on Bronchoalveolar lavage. Based on observations on biological data, temporal relationship, and clinical features, it could be inferred that the reactivation of cytomegalovirus with viral replication can predispose a person to TEN-SJS. We discuss here, in the light of the current literature, the probable association between drug-induced SJS-TEN and fulminant reactivation of cytomegalovirus.

Factors influencing uptake of influenza vaccine amongst healthcare workers in a regional center after the A(H1N1) 2009 pandemic: lessons for improving vaccination rates.

BACKGROUND: Vaccination of health-care workers (HCWs) against seasonal influenza has been consistently recommended worldwide in order to prevent nosocomial transmission and ensure delivery of health-care services during outbreaks. Overall, immunization rates were low across all nation, including among HCWs. Little is known about the acceptability and compliance with seasonal influenza vaccine among HCWs after the A(H1N1) 2009 pandemic. PARTICIPANTS AND SETTING: Between 1st and 31 January 2011, we conducted a questionnaire-based survey at the Ibn Sina regional center (Rabat, Morocco). Seven hundred twenty one HCWs have answered about their influenza immunization during the 2010/2011 season, as well as the reasons for accepting or declining this vaccine. Finally, we compare our results with previous moroccan survey. RESULTS: A total of 122 HCWs (17%) reported having received the 2010/2011 seasonal vaccine; "self-protection" and "protection of the patient" were the most frequently adduced reasons for acceptance of the influenza vaccination, whereas media controversy during the pandemic was the main argument for refusal. DISCUSSION: The post pandemic seasonal influenza vaccination coverage among the HCWs in our institution was very low. The role of media, specific attitudinal barriers and misconceptions about immunization in a global pandemic scenario is clear. The nearly constant media coverage of the A (H1N1) 2009 pandemic, reported with varying degrees of accuracy, and sometimes portraying dramatic scenarios caused some to question whether unnecessary alarm and public panic resulted. We suggest that international or national health authorities have a clear speech over looked media and to own these institutions, which will air fair and real time information about the disease.