Objective Inherited MAX gene pathogenic variants (PVs) increase risk for pheochromocytomas (PCCs) and/or paragangliomas (PGLs) in adults and children. There is little clinical experience with such mutations. This report highlights an important approach. Methods Clinical assessment, including blood chemistry, imaging studies, and genetic testing were performed. Results A 38-year-old Hispanic woman was diagnosed with PCC in 2015, treated with adrenalectomy and referred to endocrinology clinic. Notably, she presented to her primary care physician three years earlier complaining of left flank pain, intermittent diaphoresis and holocranial severe headache. We confirmed severe hypertension (180/100 mmHg) over multiple antihypertensive regimens. Biochemical and radiological studies work-up revealed high plasma metanephrine of 255 pg/mL (normal range < 65), and plasma normetanephrine of 240 pg/mL (normal range < 196). A non-contrast computed tomography scan of the abdomen revealed a 4.2 x 4.3 x 4.9 cm, round-shaped and heterogenous contrast enhancement of the left adrenal gland, and a 2-mm nonobstructive left kidney stone. A presumptive diagnosis of secondary hypertension was made. After pharmacological therapy, laparoscopic left adrenalectomy was performed and confirmed the diagnosis of pheochromocytoma. Based on both her age, family history and a high suspicion for genetic etiology, genetic testing was performed which revealed the presence of a novel likely pathogenic variant involving a splice consensus sequence in the MAX gene, designated c.64-2A> G). Conclusion The phenotype of MAX PV-related disease and paraganglioma are highlighted. The novel c.64-2A> G mutation is reported here and should be considered on the diagnostic work-up of similar cases.

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10620 Background: Up to 10% of patients with cancer harbor pathogenic germline variants (PVs) in one or more cancer susceptibility genes. Genetic cancer risk assessment (GCRA) is an important tool for the management of patients with cancer. It allows the identification of candidates for structured screening protocols, risk reduction strategies, targeted therapies and cascade testing. Knowledge about the prevalence and spectrum of PVs is limited among underrepresented populations. We studied the prevalence of germline PVs in a cohort of Mexican patients with cancer. Methods: Between April 2017 and September 2022, patients with diagnosis of cancer who met clinical criteria for GCRA according to international guidelines (NCCN) and were enrolled in the international Clinical Cancer Genomics Community Research Network (CCGCRN) registry at Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran were included. Cancer risk counseling and germline multi-gene panel testing were performed. Post-test counseling and cascade testing with known PV analysis was offered. Results: 1322 patients met inclusion criteria (probands n = 1027, relatives n = 295). Among the probands, 72.4% (744/1027) were women, median age at cancer diagnosis was 48.2 years (range 1-88) and 9.8% (n = 101) had more than one primary tumor. 14.5% (149/1027) of probands had a positive result in which 152 PV were identified ( BRCA1 n = 39, BRCA2 n = 33, ATM n = 11, CHEK2 n = 11, MLH1 n = 11, TP53 n = 7, PALB2 n = 7, NF1 n = 6, MSH2 n = 5, MSH6 n = 3, PTEN n = 3, APC n = 2, BRIP1 n = 2, CDH1 n = 2, RB1 n = 2 and 1 PV in the genes: CDKN2A, MAX, MUTYH, NBN, PTCH1, RAD50, SDHA and SDHB). The frequency of PV according to cancer diagnosis was: breast 15.5% (82/527), prostate 2% (4/198), ovarian 15.6% (12/77), colorectal 26.6% (16/60) and pancreatic 11.9% (5/42). The frequency of recurrent, potentially founder PVs in their respective genes was as follows: BRCA1 del(exons9-12) 30.7% (12/39) and CHEK2 c.707T > C 81.8% (9/11). Among the relatives referred for cascade testing the frequency of PV was 40% (118/295), 18.6% (55/295) had personal history of cancer with a median age at diagnosis of 47 years. Conclusions: Our results show a wide spectrum and a variable frequency of PVs among one of the largest examined cohorts of Mexican patients with cancer, with a high frequency of PVs among cases of breast, ovarian, and colorectal cancer. In contrast to reports from other populations, there was very low frequency of PVs among patients with prostate cancer. The outcomes of this study add to our understanding of the genetic epidemiology of cancer in the Mexican population, and support creating GCRA programs to improve access to multi-gene panel testing among underrepresented patients in limited resource settings.

Background: Breast cancer incidence is increasing globally, and a significant proportion of the disease has been linked to genetic susceptibility. Genetic knowledge and skills are essential for achieving optimal cancer care and prevention. However, in low- and middle-income countries the availability of physicians and other providers specializing in cancer genetics is very limited, and cancer genetics is not included in most undergraduate or graduate medical programs. Providing physicians-in-training with education on hereditary breast and ovarian cancer (HBOC) syndromes has the potential to improve the early identification of patients at a higher risk of breast cancer. This study aimed to assess the effect of a short HBOC course given to fellows from a single teaching hospital in Mexico City. Methods: We evaluated the basal practice patterns and knowledge on HBOC among fellows enrolled in internal medicine, general surgery, medical oncology and clinical genetics fellowship programs using a validated cancer genetics questionnaire composed of 13 questions and graded on a 0-100% scale. Fellows received a cancer genetics course (three lectures) from oncologists and geneticists with training in cancer genetics, and changes in knowledge post-course were evaluated using the same questionnaires. Descriptive statistics were utilized to describe the included subjects, and T-tests were used to compare pre and post questionnaire scores. Results: 110 fellows with a median age of 26.9 years (range 24-31) completed the basal questionnaire. 48.9% were enrolled in internal medicine, 21.8% in general surgery, 13.6% in medical oncology and 7.2% in clinical genetics. All respondents reported to routinely interrogate patients about their family history of cancer, and 70% said they had referred patients to the genetics clinic at their institution. The average score on the basal survey was 62% (SD 17). After the cancer genetics course was completed, 85 fellows answered the questionnaire. We found a relative increase in knowledge from pre to post-intervention of 12% (post-intervention average score 70% [SD 14]), which was statistically significant (p <0.01). After the course, 36% of fellows said they would feel capable to provide recommendations to patients at risk of HBOC, compared to 17% before the course (p <0.01). Conclusions: Although knowledge about HBOC among Mexican fellows is suboptimal, we found that providing short educational courses on cancer genetics may lead to a significant increase in knowledge on HBOC, as well as to an increase in confidence regarding recommendations. This study reinforces the need to develop focused and cost-effective educational strategies in low- and middle-income countries where specialists in cancer genetics are scarce, in order to provide physicians-in-training with knowledge and tools to recognize, refer, and counsel patients at risk of HBOC. Citation Format: Yanin Chavarri Guerra, Hector De la Mora Molina, Rosa Elena Caballero Landinez, Arantxa Lagunas Salazar, Andrea De la O Murillo, Rafael Reyes Arciniega, Enrique Soto Perez de Celis, Jose Luis Rodriguez Olivares, Osvaldo M Mutchinick, Jazmin Arteaga Vazquez. An educational cancer genetics course to increase knowledge on hereditary breast cancer syndromes among physicians-in-training at a teaching hospital in Mexico City [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-15-02.

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