Familial pancreatic cancer associated to germline mutation of BRCA2

Sánchez Bermúdez, Ana Isabel; Marín Zafra, Gema; Sarabia Meseguer, M. Desamparados

doi:10.1016/j.medcle.2018.02.010

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Desamparados Sarabia Meseguer" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Ana Isabel" "apellidos" => "Sánchez Bermúdez" "email" => array:1 [ 0 => "Ana.sanchez.bermudez@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Gema" "apellidos" => "Marín Zafra" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "M. Desamparados" "apellidos" => "Sarabia Meseguer" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Análisis Clínicos, Laboratorio de Diagnóstico Genético, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Oncología Médica, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Cáncer de páncreas familiar asociado a mutación en el gen BRCA2" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1419 "Ancho" => 2159 "Tamanyo" => 99398 ] ] "descripcion" => array:1 [ "en" => "Family tree of the patient-carriers of the germline mutation in BRCA2 c.3455T>G. +: carrier of the mutation; −: non-carrier; BC: breast cancer; OC: ovarian cancer; PC: pancreatic cancer. The arrow indicates the index case. The numbers next to the symbol indicate the age at diagnosis." ] ] ] "textoCompleto" => "At least 5–10% of all cases of pancreatic adenocarcinomas have a familial history of pancreatic cancer. Pancreatic cancer can be associated with hereditary breast and ovarian cancer (HBOC), caused by germline mutations in BRCA1 and BRCA2 (breast and ovarian cancer predisposition gene).<a class="elsevierStyleCrossRef" href="#bib0025">1</a> This paper presents the finding of 2 consecutive generations of a Spanish family with several cases of pancreatic cancer, as well as other tumours, including breast cancer.A 74-year-old man presented with a retroareolar mass in the right breast. The biopsy established that it was a high-grade infiltrating ductal carcinoma (IDC) with positive oestrogen receptors, negative progestogens, negative HER2/neu, 20% Ki-67 proteins and positive E-cadherin. A right mastectomy was performed with dissection of axillary nodes (stage T1N0M0). Four months later, the patient experienced an elevation of liver enzymes and PET revealed an increase in metabolism in the head of the pancreas suggestive of a tumour mass. The CT scan confirmed an infiltrating mass in the head of the pancreas (T4N1M0). The case was referred to the genetic counselling clinic where the family history was collected (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Given the multiple cases of PC and the male breast cancer case, it was decided to study the BRCA2 gene. After genetic counselling and signing the informed consent, a peripheral blood sample was taken from the patient. The DNA was extracted according to the standardized protocols and the genetic test was performed through next-generation sequencing (NGS) on the GS Junior system from Roche®. A mutation was detected in exon 11 of the BRCA2 gene (c.3455T>G). It is a nonsense mutation coding for a stop codon, resulting in a truncated protein, probably non-functional since it loses several fundamental domains for the development of its cellular activity. The variant c.3455T>G has been described in families with breast cancer and/or hereditary ovarian cancer on 2 occasions by the Breast Cancer Information Core (BIC) database.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>There are several reasons why it is important to know the genotype of these families. It is essential to know the increased risk for PC that mutation carriers have, as well as to identify non-carrier individuals and thus reduce their anxiety state. Compared with the general population, carriers of BRCA2 mutations have 3.5 times more risk of developing PC (95% CI: 1.9–6.6).<a class="elsevierStyleCrossRef" href="#bib0030">2</a> Another important reason is the potential development of new treatments such as inhibitors of the enzyme poly (ADP ribose) polymerase (PARP-1). In BRCA-deficient cells, inhibition of the alternative DNA repair route (where the enzyme PARP-1 plays an important role) results in greater sensitivity to certain chemotherapeutic agents that cause DNA damage such as mitomycin-C, cisplatin, chlorambucil and melphalan.<a class="elsevierStyleCrossRef" href="#bib0035">3</a> Finally, it should be noted that in families with familial pancreatic cancer and a known mutation, screening is complex due to the lack of data confirming a proven benefit. The tumour markers (CA 19.9 and CEA) provide low sensitivity and specificity for the early detection of lesions. CT has good sensitivity for the detection of pancreatic lesions larger than 2cm with the associated risk of radiation.<a class="elsevierStyleCrossRef" href="#bib0040">4</a> Endoscopic ultrasound is a good technique for clinical and histological diagnosis since it allows a pathologic study of lesions suspected of malignancy and the visualization of small pancreatic masses. At present, abdominal MRI is an interesting diagnostic test because of its sensitivity and specificity in the detection of pancreatic lesions, without the radiation-associated risk.In summary, it can be confirmed that the BRCA genes are good candidates to evaluate the genetic susceptibility of patients with familial pancreatic cancer where the phenotype of breast and ovarian cancer is present. They can even play an important role in the treatment of the disease, as well as in the screening of family members carrying pathogenic variants." "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Sánchez Bermúdez AI, Marín Zafra G, Sarabia Meseguer MD. Cáncer de páncreas familiar asociado a mutación en el gen BRCA2. Med Clin (Barc). 2018;150:e19–e20." ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1419 "Ancho" => 2159 "Tamanyo" => 99398 ] ] "descripcion" => array:1 [ "en" => "Family tree of the patient-carriers of the germline mutation in BRCA2 c.3455T>G. +: carrier of the mutation; −: non-carrier; BC: breast cancer; OC: ovarian cancer; PC: pancreatic cancer. The arrow indicates the index case. The numbers next to the symbol indicate the age at diagnosis." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:4 [ 0 => array:3 [ "identificador" => "bib0025" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genetic susceptibility to pancreatic cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "A.P. Klein" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/mc.20855" "Revista" => array:6 [ "tituloSerie" => "Mol Carcinog" "fecha" => "2012" "volumen" => "51" "paginaInicial" => "14" "paginaFinal" => "24" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22162228" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0030" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cancer risks in BRCA2 mutation carriers" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "Breast Cancer Linkage Consortium" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "J Natl Cancer Inst" "fecha" => "1999" "volumen" => "91" "paginaInicial" => "1310" "paginaFinal" => "1316" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10433620" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0272638616000184" "estado" => "S300" "issn" => "02726386" ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0035" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A synthetic lethal therapeutic approach: poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "A. Ashworth" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Clin Oncol Off J Am Soc Clin Oncol" "fecha" => "2008" "volumen" => "26" "paginaInicial" => "3785" "paginaFinal" => "3790" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0040" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Imaging diagnosis of pancreatic cancer: a state-of-the-art review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "E.S. Lee" 1 => "J.M. Lee" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3748/wjg.v20.i24.7864" "Revista" => array:6 [ "tituloSerie" => "World J Gastroenterol" "fecha" => "2014" "volumen" => "20" "paginaInicial" => "7864" "paginaFinal" => "7877" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24976723" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack345350" "titulo" => "Acknowledgement" "texto" => "We thank the Spanish Clinical Laboratory Association (AEFA) for their help through the post-residency grant to Ana Isabel Sánchez Bermúdez." 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Vol. 150. Issue 8.

Pages e19-e20 (April 2018)

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