BRCA1 and BRCA2 germline mutation analysis among Indian women from south India: identification of four novel mutations and high-frequency occurrence of 185delAG mutation

Mutations in the BRCA1 and BRCA2 genes profoundly increase the risk of developing breast and/or ovarian cancer among women. To explore the contribution of BRCA1 and BRCA2 mutations in the development of hereditary breast cancer among Indian women, we carried out mutation analysis of the BRCA1 and BRCA2 genes in 61 breast or ovarian cancer patients from south India with a positive family history of breast and/or ovarian cancer. Mutation analysis was carried out using conformation-sensitive gel electrophoresis (CSGE) followed by sequencing. Mutations were identified in 17 patients (28.0%); 15 (24.6%) had BRCA1 mutations and two (3.28%) had BRCA2 mutations. While no specific association between BRCA1 or BRCA2 mutations with cancer type was seen, mutations were more often seen in families with ovarian cancer. While 40% (4/10) and 30.8% (4/12) of families with ovarian or breast and ovarian cancer had mutations, only 23.1% (9/39) of families with breast cancer carried mutations in the BRCA1 and BRCA2 genes. In addition, while BRCA1 mutations were found in all age groups, BRCA2 mutations were found only in the age group of <= 40 years. Of the BRCA1 mutations, there were three novel mutations (295delCA; 4213T -> A; 5267T -> G) G) and three mutations that have been reported earlier. Interestingly, 185delAG, a BRCA1 mutation which occurs at a very high frequency in Ashkenazi Jews, was found at a frequency of 16.4% (10/61). There was one novel mutation (4866insT) and one reported mutation in BRCA2. Thus, our study emphasizes the importance of mutation screening in familial breast and/or ovarian cancers, and the potential implications of these findings in genetic counselling and preventive therapy.

A playful side to twelfth-century mathematics

As editors of the book Lilavati's Daughters: The Women Scientists of India, reviewed by Asha Gopinathan (Nature 460, 1082; 2009), we would like to elaborate on the background to its title. Lilavati was a mathematical treatise of the twelfth century, composed by the mathematician and astronomer Bhaskaracharya (1114–85) — also known as Bhaskara II — who was a teacher of repute and author of several other texts. The name Lilavati, which literally means 'playful', is a surprising title for an early scientific book. Some of the mathematical problems posed in the book are in verse form, and are addressed to a girl, the eponymous Lilavati. However, there is little real evidence concerning Lilavati's historicity. Tradition holds that she was Bhaskaracharya's daughter and that he wrote the treatise to console her after an accident that left her unable to marry. But this could be a later interpolation, as the idea was first mentioned in a Persian commentary. An alternative view has it that Lilavati was married at an inauspicious time and was widowed shortly afterwards. Other sources have implied that Lilavati was Bhaskaracharya's wife, or even one of his students — raising the possibility that women in parts of the Indian subcontinent could have participated in higher education as early as eight centuries ago. However, given that Bhaskara was a poet and pedagogue, it is also possible that he chose to address his mathematical problems to a doe-eyed girl simply as a whimsical and charming literary device.