Molecular Endocrinology


Branca Cavaco

Principal Investigator



Campus IPO
Instituto Português de Oncologia de Lisboa Francisco Gentil EPE
Unidade Investigação Patobiologia Molecular
Rua Prof. Lima Basto
1099-023 - Lisboa - Portugal

(+351) 217 229 800 (ext. 1762)
(+351) 217 229 818
Fax: (+351) 217 229 895
E-mail: bcavaco(at)

The main aim of our research is to elucidate the molecular mechanisms involved in the aetiology and progression of sporadic and familial forms of thyroid and parathyroid tumours.

Research Areas

Our main challenge, at the moment, is to elucidate two clinically important topics related to thyroid cancer:

To map and identify genes predisposing to familial thyroid cancer, using recently developed technologies, such as single nucleotide polymorphisms (SNP)-arrays (Fig.1), and whole-exome sequencing.
The identification of causative gene(s) will enable families to undergo early diagnosis and may lead to the development of new effective therapies for this disease (Fig.2).

To identify new therapeutic targets for poorly-differentiated and undifferentiated thyroid carcinomas using as strategies the microarray technology, sequencing of candidate genes, and functional characterization in vitro and in vivo models.
Deciphering the mechanisms underlying the progression to the more advanced cases of thyroid cancer, will help to design new therapies for these aggressive and almost untreatable neoplasias.

Our research activities are also focused in the familial predisposition to parathyroid-related endocrine diseases that principally affect calcium and phosphate homeostasis:

To study the familial predisposition to parathyroid-related endocrine neoplasia diseases, such as the multiple endocrine neoplasia type 1 (MEN1), and the hereditary hyperparathyroidism and jaw tumour (HPT-JT) syndromes. Since 1997, our group has centralised the collection, registry, and the molecular diagnosis of MEN-1 and HPT-JT cases, identified in Endocrinology Departments in Portugal.

To study patients with familial endocrine syndromes, that affect calcium and phosphate homeostasis, resulting in hipo/hipercalcemia-related manifestations. We study the pseudohypoparathyroidism type Ib (PHP-Ib), the familial hypocalciuric hypercalcemia/neonatal severe hyperparathyroidism (FHH/NSHPT), and the autosomal dominant hypoparathyroidism (ADH). The clinical and genetic characterization of these patients is expected to lead to advances in our understanding of these diseases.


“Identification of genes involved in familial thyroid cancer using the new Single Nucleotide Polymorphisms (SNP)-Arrays and Large Scale Resequencing technologies”.
Principal Investigador: Branca Cavaco
NRS Liga Portuguesa Contra o Cancro - Terry Fox, 2009-2012

“Identification of novel genes associated with the development of sporadic medullary thyroid carcinoma”
Principal Investigador: Valeriano Leite
Entidade financiadora: IPOLFG, EPE; SPEDM/Genzyme em Patologia da Tiróide; 2010-2013

“Evaluation of CDKN3, ESRP1 AND ESRP2 genes as potential new targets for the treatment of anaplastic thyroid carcinomas”.
Principal Investigador: Branca Cavaco
Sociedade Portuguesa de Endocrinologia, Diabetes e Metabolismo (SPEDM), 2011-2013

Prizes and Awards

Prizes Banca Cavaco

Selected Publications

Selected Publications

  • “FOXE1 polymorphisms are associated with familial and sporadic nonmedullary thyroid cancer susceptibility. Clinical Endocrinology (Oxf)”
    Tomaz R.A., Sousa I., Silva J.G., Santos C., Teixeira M.R., Leite V., Cavaco B.M.
    Clinical Endocrinology (Oxf). 77:926-933 (2012) (doi:10.1111/j.1365-2265.2012.04505.x.).
  • “S-phase fraction and ploidy as predictive markers in primary disease and recurrence of papillary thyroid carcinoma”
    Pinto A.E., Silva G.L., Pereira T., Cabrera R.A., Santos J.R., Leite V.
    Clin Endocrinol (Oxf). 77:302-309 (2012).
  • “Identification of the first germline HRPT2 whole-gene deletion in a patient with primary hyperparathyroidism”.
    Domingues R., Tomaz R.A., Martins C., Nunes C., Bugalho M.J., Cavaco B.M.
    Clinical Endocrinology (Oxf). 76:33-38 (2012) (doi: 10.1111/j.1365-2265.2011.04184.x.)
  • “Identification of de novo germline mutations in the HRPT2 gene in two apparently sporadic cases with challenging parathyroid tumor diagnoses”
    Cavaco B.M., Santos R., Félix A., Carvalho D., Lopes J.M., Domingues R., Sirgado M., Rei N., Fonseca F., Santos J.R., Sobrinho L., Leite V.
    Endocrine Pathology 22:44–52 (2011).
  • “High Prevalence of RAS Mutations in RET-Negative Sporadic Medullary Thyroid Carcinomas”
    Moura M.M., Cavaco B.M., Pinto A.E., Leite V.
    The Journal of Clinical Endocrinology and Metabolism 96: E863–E868 (2011).
  • “Differential Methylation as a Cause of Allele Dropout at the Imprinted GNAS Locus”
    Tomaz R.A., Cavaco B.M., Leite V.
    Genetic Testing and Molecular Biomarkers 14:455-460 (2010).
  • “Clinical and genetic characterization of Portuguese patients with pseudohypoparathyroidism type Ib”
    Cavaco B.M., Tomaz R.A., Fonseca F., Mascarenhas M.R., Leite V., Sobrinho L.G.
    Endocrine 37:408–414 (2010).
  • “Gene expression profiling associated with the progression to poorly differentiated thyroid carcinomas”
    Pita J.M., Banito A., Cavaco B.M., Leite V.
    British Journal of Cancer 101:1782-1791 (2009).
  • “Correlation of RET somatic mutations with clinicopathological features in sporadic medullary thyroid carcinomas”
    Moura M.M., Cavaco B.M., Pinto A.E., Domingues R., Santos J.R., Cid M.O., Bugalho M.J., Leite V.
    British Journal of Cancer 100:1777-1083 (2009).
  • “Mapping a New Familial Thyroid Epithelial Neoplasia Susceptibility Locus to Chromosome 8p23.1-p22 by High-Density Single-Nucleotide Polymorphism Genome-Wide Linkage Analysis”
    Cavaco B.M., Batista P.F., Sobrinho L.G., Leite V.
    The Journal of Clinical Endocrinology and Metabolism 93:4426-4430 (2008).
  • “Familial non-medullary thyroid carcinoma: analysis of fPTC/PRN, NMTC1, MNG1 and TCO susceptibility loci and identification of somatic BRAF and RAS mutations”
    Cavaco B.M., Batista P.F., Martins C., Banito A., Rosário F., Limbert E., Sobrinho L.G., Leite V.
    Endocrine-Related Cancer 15:207-215 (2008).
  • "Caution should be used when interpreting alterations affecting the exon 3 of the BRCA2 gene in breast/ovarian cancer families".
    Machado P.M., Cavaco B. M., Brandão R.D., Eugénio J., Santos S., Opinião A., Vaz F.
    Letter to: Journal of Clinical Oncology 25:5035-5038 (2007).
  • "Screening for a BRCA2 rearrangement in high-risk breast/ovarian cancer families: evidence for a founder effect and analysis of the associated phenotypes".
    Machado P.M., Brandão R.D., Cavaco B.M., Eugenio J., Bento S., Nave M., Rodrigues P., Fernandes A., Vaz F.
    Journal of Clinical Oncology 25(15):2027-34 (2007).
  • "Pax8PPARgamma stimulates cell viability and modulates expression of thyroid-specific genes in a human thyroid cell line".
    Espadinha C., Cavaco B.M., Leite V.
    Thyroid 17(6):497-509 (2007).
  • "Expression and function of the chemokine receptor CCR7 in thyroid carcinomas".
    Sancho M., Vieira J.M., Casalou C., Mesquita M., Pereira T., Cavaco B.M., Dias S., Leite V.
    Journal of Endocrinology 191:229-238 (2006).
  • “PARAFIBROMIN mutations in hereditary hyperparathyroidism syndromes and parathyroid tumours”
    Bradley K.J., Cavaco B.M., Bowl M.R., Harding B., Cranston T., Fratter C., Besser G.M., Conceição Pereira M., Davie M.W., Dudley N., Leite V., Sadler G.P., Seller A., Thakker R.V.
    Clinical Endocrinology (Oxf) 64:299-306 (2006).
  • “Expression of vascular endothelial growth factor (VEGF) and its receptors in thyroid carcinomas of follicular origin: a potential autocrine loop”.
    Vieira J.M., Rosa Santos S.C., Espadinha C., Correia I., Vag T., Casalou C., Cavaco B.M., Catarino A.L., Dias S., Leite V.
    European Journal of Endocrinology 153:701-709 (2005).
  • “Utilisation of a cryptical non-canonical donor splice site of the gene encoding PARAFIBROMIN is associated with familial isolated primary hyperparathyroidism”
    Bradley K.J., Cavaco B.M., Bowl M.R., Harding B., Young A., Thakker R.V.
    Journal of Medical Genetics 42: e51 (2005).
  • “Uterine tumours are a phenotypic manifestation of the hyperparathyroidism-jaw tumour syndrome”
    Bradley K.J., Hobbs M.R., Buley I.D., Carpten, J.D., Cavaco B.M., Fares, J.E., Laidler P., Manek S., Robbins C.M., Salti I.S., Thompson N.W., Jackson C.E., Thakker R.V.
    Journal of Internal Medicine 257:18-26 (2005).
  • “A study of MECT1-MAML2 in mucoepidermoid carcinoma and Warthin’s tumor of salivary glands”
    Martins C., Cavaco B., Tonon G., Kaye F.J., Soares J., Fonseca I.
    Journal of Molecular Diagnostics 6:205-210 (2004).
  • “Hyperparathyroidism-jaw tumor syndrome in Roma families from Portugal is due to a founder mutation of the HRPT2 gene”
    Cavaco B.M., Guerra L., Bradley K.J., Carvalho D., Harding B., Oliveira A., Santos M.A., Sobrinho L. G., Thakker R.V. & Leite V.
    The Journal of Clinical Endocrinology & Metabolism 89:1747-1752 (2004).
  • “Multiple endocrine neoplasia type 1 (MEN1) germline mutations in familial isolated primary hyperparathyroidism”
    Pannett A.A., Kennedy A.M., Turner J.J., Forbes S.A., Cavaco B.M., Bassett J.H., Cianferotti L., Harding B., Shine B., Flinter F., Maidment C.G., Trembath R., Thakker R.V.
    Clinical Endocrinology (Oxf) 58:639-646 (2003).
  • “Preoperative diagnosis of suspicious parathyroid adenomas by RT-PCR using mRNA extracted from leftover cells within a needle used for ultrasonically guided fine needle aspiration cytology”
    Cavaco B., Torrinha F., Mendonça E., Pratas S., Boavida J., Sobrinho L.G., Leite V.
    Acta Cytologica 47:5-12 (2003).
  • “HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome”
    J.D. Carpten, C.M. Robbins, A.Villablanca, L. Forsberg, S. Presciuttini, J. Bailey-Wilson, W.F. Simonds, E.M. Gillanders, A.M. Kennedy, J.D. Chen, S.K. Agarwal, R. Sood, M.P. Jones, T.Y. Moses, C. Haven, D. Petillo, P.D. Leotlela, B. Harding, D. Cameron, A.A. Pannett, A. Hoog, H. Heath 3rd, L.A. James-Newton, B. Robinson, R.J. Zarbo, B.M. Cavaco, W. Wassif, N.D. Perrier, I.B. Rosen, U. Kristoffersson, P.D. Turnpenny, L.O. Farnebo, G.M. Besser, C.E. Jackson, H. Morreau, J.M. Trent, R.V. Thakker, S.J. Marx, B.T. Teh, C. Larsson, M.R. Hobbs.
    Nature Genetics 32:676-680 (2002).
  • "Mutational analysis of Portuguese families with Multiple Endocrine Neoplasia Type 1 reveals large germline deletions"
    Cavaco B.M., Domingues R., Bacelar M.C., Cardoso H., Barros L., Gomes L., Ruas M.M.A., Agapito A., Garrão A., Pannett A.A.J., Silva J.L., Sobrinho L.G., Thakker R.V., Leite V.
    Clinical Endocrinology 56:465-473 (2002).
  • “Clonal origin of non-medullary thyroid tumours assessed by non-random X-chromosome inactivation”
    Moniz S., Catarino A.L., Marques A.R., Cavaco B., Sobrinho L., Leite V.
    European Journal of Endocrinology 146:1-7 (2002).
  • “Medullary carcinomas of the thyroid: monoclonal origin”
    Marques A.R., Catarino A.L., Moniz S., Cavaco B., Roque L., Sobrinho L., Leite V.
    Thyroid 11:1109-1113 (2001).
  • “Hypoglycaemia due to the insulin autoimmune syndrome: report of two cases with characterisation of HLA alleles and insulin autoantibodies”
    Cavaco B., Uchigata Y., Porto T., Santos M.A., Sobrinho L., Leite V.
    European Journal of Endocrinology 145:311-316 (2001).
  • “Studies of the hyperparathyroidism-jaw tumour (HPT-JT) syndrome in a kindred from Portugal”
    Cavaco B., Barros L., Pannett A.A.J., Ruas L., Carvalheiro M., Ruas M.M.A., Krausz T., Santos M.A., Sobrinho L.G., Leite V., Thakker R.V.
    Quarterly Journal of Medicine 94:213-222 (2001).
  • “Spontaneously occurring anti-PTH autoantibodies must be considered in the differential diagnosis of patients with elevated serum PTH levels”
    Cavaco B., Leite V., Loureiro M.M., Ferreira M.F., Pereira M.C., Santos M.A., Sobrinho L.G.
    Journal of Endocrinological Investigation 22:829-834 (1999).
  • “Hyperprolactinemia due to big big prolactin is differently detected by commercially available immunoassays”
    Cavaco B., Prazeres S., Santos M.A., Sobrinho L.G., Leite V.
    Journal of Endocrinological Investigation 22:203-208 (1999).
  • “Mapping the gene causing hereditary primary hyperparathyroidism in a Portuguese kindred to chromosome 1q22-q31”
    Williamson C, Cavaco B M, Jausch A, Dixon P H, Forbes S, Harding B, Holtgreve-Grez H, Schoell B, Pereira M C, Font A P, Loureiro M M, Sobrinho L.G., Santos M.A. and Thakker R.V.
    Journal of Bone and Mineral Research 14:230-239 (1999).
  • "Some forms of Big Big prolactin behave as a complex of monomeric prolactin with an immunoglobulin G in patients with macroprolactinemia or prolactinoma"
    Cavaco B., Leite V., Santos M.A., Arranhado E., Sobrinho L.G.
    Journal of Clinical Endocrinology and Metabolism 80:2342-2346 (1995).


Prof. R. V. Thakker, MD, PhD,
Academic Endocrine Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism,
Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK

Prof. Manuel Teixeira, MD, PhD,
Research Centre of the Portuguese Oncology Institute, Porto, PT

Prof. Graham Williams, MD, PhD,
Molecular Endocrinology Laboratory, Department of Medicine and MRC Clinical Sciences Centre, Hammersmith Campus, London, UK.

Prof. Harald Jüppner, MD, PhD,
Endocrine Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

Team photos