Frequency of anaplastic lymphoma kinase rearrangements in Moroccan patients with non small cell lung cancer: a multi-institutional national retrospective study.

BACKGROUND: Anaplastic lymphoma kinase (ALK) rearrangement is a predictive factor of response to ALK inhibitors in non small cell lung cancer (NSCLC). The prevalence of ALK rearrangements is well known in Whites and Asians. However, data identifying the frequency of this rearrangement in Moroccan and North African population are lacking. The objective of this study is to report the frequency of ALK rearrangement in a group of Moroccan patients with NSCLC. METHODS: A retrospective study was performed enrolling 120 Moroccan patients with NSCLC whose biopsy samples were tested for ALK rearrangement in order to identify the frequency of ALK rearrangement and its potential association with selected variables. The ALK testing was established using fluorescent in situ hybridization (FISH) or immunohistochemistry (IHC). RESULTS: The frequency of ALK rearrangement was 4.2% (5/120). All positive cases were males with advanced adenocarcinoma. ALK rearrangements prevalence was significantly higher in older patients. CONCLUSIONS: The frequency of ALK rearrangements among the Moroccan population tends to correlate with the average frequency reported worldwide, with some specific features. Further prospective studies with larger patients' numbers are needed to verify these findings.

Frequency and types of EGFR mutations in Moroccan patients with non-small cell lung cancer.

BACKGROUND: Mutations in the epidermal growth factor receptor (EGFR) gene are commonly observed in non-small cell lung cancer (NSCLC), particularly in adenocarcinoma histology. The frequency of EGFR mutations is ethnicity-dependent, with a higher proportion reported in Asian populations than Caucasian populations. There is a lack of data on these mutations in north Africa. METHODS: Tumor specimens from Moroccan patients with NSCLC were collected from five pathology laboratories between November 2010 and December 2017 to determine frequency and types of EGFR mutations. Tumors were tested in a reference center for EGFR by polymerase chain reaction and sequencing of exons 18, 19, 20, and 21. RESULTS: A total of 334 patients were enrolled: 242 (72.5%) males and 92 females (27.5%). A total of 56.9% had a history of smoking. EGFR testing of the 334 lung adenocarcinoma samples demonstrated a wild-type EGFR in 261 (78.1%) and mutated EGFR in 73 (21.9%). Mutations were mainly detected in the exon 19 deletion (65.8%), followed by exon 21 L858 (17.8%) and other exon 21 codon mutations (5.5%) and exon 18 (6.8%), whereas primary mutations of exon 20 were less frequent (4.1%). In patients with advanced NSCLC, the detection of EGFR mutation was independently associated with sex (41.3% female vs 14.5% male; p < 0.001) and smoking status (34.8% nonsmokers vs 12.9% active smokers; p < 0.001). The mean age was significantly different between the two groups (p = 0.041). CONCLUSION: Our findings confirm the genetic heterogeneity of NSCLC worldwide, reporting frequency of EGFR mutations in Moroccan patients with NSCLC between those of Asian and Caucasian populations.

The Frequency and Specific Features of Rare Epidermal Growth Factor Receptor Mutations in Moroccan Patients with Lung Adenocarcinoma whose Tumors harbor positive EGFR mutations.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations are a heterogeneous group of genetic alterations mainly identified in lung adenocarcinoma (AC). They occur in exon 18 to 20 of the EGFR gene. Common EGFR mutations are deletions in exon 19 and substitutions in exon 21, while mutations in exon 18 and exon 20 are rare. Their response to tyrosine kinase inhibitors (TKI) is different, common EGFR mutations are more sensitive to TKI with better response rate and survival, whereas rare EGFR mutations are TKI resistant with poor prognosis and clinical outcomes. The objective of the present study was to report the frequency and characteristics of rare EGFR mutations in a group of Moroccan patients with lung AC harboring a positive EGFR mutation. PATIENTS AND METHODS: All cases of Moroccan patients with lung AC harboring mutated EGFR were collected from 334 EGFR test requested. Common EGFR mutations were defined as deletions in exon 19 and substitutions in exon 21 while mutation in exons 18 and 20 were qualified as rare EGFR mutations. Patients' characteristics were reported and compared between the two groups of common and rare EGFR mutations. RESULTS: EGFR mutations were positive in 73/334 of all requested tests. Common EGFR mutations accounted 89% (65/73). Rare EGFR mutations were present in 8 cases (11%). Rare EGFR mutations were composed of 62.5% exon 18 mutations (5/8) and 37.5% exon 20 mutation (3/8). The frequency of regular smokers in patients with tumors expressing rare EGFR mutations was significantly higher than that found in patients with tumors having common EGFR mutations (p=0.013). DISCUSSION: The frequency found in the present study was consistent with the literature data. However, we found that rare EGFR mutations occurred mostly in exon 18 rather than exon 20, findings that are discordant with the available literature. Thus, we could suggest that Moroccan patients with rare EGFR mutations would benefit more from TKI treatment. CONCLUSION: Rare EGFR mutations are a heterogeneous subset of genetic alterations in lung AC. Their study deserves a real relevant interest. Some one tenth of lung AC tumors in Moroccan patients harbor a rare EGFR mutation. Further prospective studies are needed, in larger numbers of patients, to assess their specific characteristics and outcomes.

Frequency and Spectrum of KRAS Mutations in Moroccan Patients with Lung Adenocarcinoma.

Background. In lung adenocarcinoma, the frequency of KRAS mutations is ethnicity dependent with a higher proportion in African Americans and white Caucasians than in Asians. The prevalence of these mutations among North Africans patients is unknown. The objective of this study was to report the frequency and spectrum of KRAS mutations in a group of Moroccan lung adenocarcinoma patients. Methods. Tumor specimens from 117 Moroccan patients with lung adenocarcinoma were selected to determine frequency and spectrum of KRAS mutations. KRAS mutations in codons 12 and 13 of exon 2 were analyzed using conventional DNA sequencing. Results. The overall frequency of the KRAS mutations was 9% (11/117). In the population with KRAS mutations, there was a trend towards more male (P = 0.06) and more smokers (P = 0.08) compared to patients with wild type KRAS. KRAS mutations were located at codon 12 in 10 out of 11 patients (91%). The G12C mutation was the most frequent KRAS mutation (73%). Conclusion. This is the first study to date examining the frequency and spectrum of KRAS mutations in lung adenocarcinomas in North African and Arab populations. KRAS mutation frequency in Moroccan patients was comparable with the frequency observed in East-Asian population. KRAS mutations are more likely observed in males and smokers and to be transversions. Further studies, in larger numbers of patients, are needed to confirm these findings.

Frequency and type of epidermal growth factor receptor mutations in moroccan patients with lung adenocarcinoma.

INTRODUCTION: Epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer predict response to tyrosine kinase inhibitors. The frequency of EGFR mutations is ethnicity-dependent, with a higher proportion in Asian populations than in whites. The prevalence of these mutations among North African patients is unknown. The objective of this study was to report the frequency and spectrum of EGFR mutations in a group of Moroccan patients with lung adenocarcinoma (AC). METHODS: Tumor specimens from 137 Moroccan patients with lung AC were selected to determine frequency and spectrum of EGFR mutations. Mutation detection techniques were polymerase chain reaction amplification and sequencing of exons 18, 19, 20, and 21. RESULTS: The overall frequency of the EGFR mutation was 21%. Mutations were mainly detected in the exon 19 (69%), followed by exon 21 (21%) and exon 20 (7%), whereas mutations in the exon 18 were rare (3%). EGFR mutation rate was significantly higher in women and in never smokers. CONCLUSION: Some one fifth of lung AC tumors in Moroccan patients harbor EGFR mutations. This mutation frequency is higher than that found in whites but lower than in Asian population. Further studies, in larger numbers of patients, are needed to confirm these findings.